The Human Cerebral Cortex

The human cerebrum accounts for roughly 80% of total brain mass and is essential for language, cognition, memory, consciousness, and awareness of surrounding. In this article, our main focus is the cortex, the outer layer of the cerebrum, which is responsible for voluntary movements and cognitive functions. Generally, you can establish the idea that the cortex has three functioning areas- sensory, association, and motor areas, and is characterized into four regions, or lobes- frontal, temporal, occipital, and parietal lobes.

Before I confuse you with the different lobes of the cerebral cortex, let’s first talk about how the cerebral cortex receives and processes sensory information. Since we are still not familiar with the processing of memory and all that, scientists can only focus on the study of sensory information, which they developed through a method called functional imaging, brain scanning that assists the  observation of active brain regions in response to a certain stimulus. Hence, let’s only deal with sensory information for now.

The human cerebral cortex receives sensory information from two sources. The first is somatosensory receptors (soma=body). Somatosensory receptors are “body” receptors that provide information about touch, pain, pressure, temperature, and the position of muscles and limbs. The other is sensory organs such as the eyes and nose, which clusters of receptor neurons are organized. Most sensory information coming into the cortex is directed via the thalamus to primary sensory areas within the brain lobes, which is then passed along to nearby association areas where processes of sensory input take place. 

Now that we’ve talked about how and where sensory information is received, let’s take a brief view on the lobes of the cerebral cortex. Generally, the parietal, temporal, and occipital lobes are regions that deal with specific sensory information (auditory, touch, visual, odor, etc.), whereas the frontal lobe carries out processed information into action (movement). When constructing this concept in your brain, be sure to realize that every lobe consists of two parts, left and right, and the left and right side may have different functions that are not illustrated in the figure. For instance, the temporal lobe is responsible for the processing of both auditory, odor, etc., so don’t let the figure below limit your understanding. In addition, the parietal, temporal, and occipital lobes have what we characterized as “primary sensory areas” and “association areas,” which correlates with what we’ve mentioned about the receiving and processing of information in the prior paragraph. Keep in mind that these “areas” are defined through functional imaging (brain scanning); in other words, these areas are active when information is received and processed. And that’s all we know. In summary, what we’ve discussed is only the broad, general view regarding the functions of the lobes. The frontal lobe, for instance, plays other roles, such as managing memory; however, this subject, as well as many others, are still too blur for us to fully grasp. As a result, the idea above is pretty much what you should know, unless you are interested in pursuing neuroscience. It would be useful if you can draw and organize the above information yourself, so it is integrated into your mind.

Reference:

Campbell, et al. Biology: A Global Approach. 11th ed., Pearson, 2017.

An Update on the Coronavirus

As all kinds of news and information are being exposed to people, a clear comprehension must be made, particularly about what the coronavirus (COVID-19) really is, its pervasiveness and effects on the worldwide population, as well as potential post-infectious diseases.

To make it easy for all to understand, the virus is often being commonly referred to as the “coronavirus” or “COVID-19.” However, that is not the case. COVID-19 is the abbreviation for the term “coronavirus disease 2019”. The virus that causes all this chaos, meanwhile, is coined the name “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2). This virus, which is similar to the SARS-CoV in many aspects, differs in some major structures. Anyway, both of them are types of coronaviruses, and in this article, let’s still refer to the SARS-CoV-2 as the coronavirus, for the sake of concision. 

Typical coronavirus symptoms include coughing, fever, and shortness of breath. Since such symptoms are not indicative of lung infection, or pneumonia, people who are infected with the coronavirus very often do not have pneumonia. The majority of COVID-19 cases, in fact, are mild and only a small percentage of patients will require hospitalization. It is true, however, that COVID-19 can lead to pneumonia for some patients, especially those over the age of 60 and those with pre-existing lung diseases, such as asthma, emphysema, or any form of fibrosis, which make them prone to the development of pneumonia. This explains why the number of deaths in Italy soar above that of many other countries (Italy has an elderly population of roughly 23%).

According to the statistics provided by the World Health Organization (WHO), currently over 99,027 patients have recovered from the COVID-19 infection. However, multiple sources, such as doctors from Taiwan and Hong Kong, suggest that there are roughly 3%-5% of chances for patients who recovered from the coronavirus infection to be found with post-infectious diseases, most likely pulmonary fibrosis. Pulmonary fibrosis is a condition in which the lungs become scarred and tissues around and between the alveoli thickens over time, in this case, due to the repairing of the lungs after the coronavirus infection. Fibroblasts, which are responsible for the repairing of the lungs, tend to synthesize abundant amounts of extracellular matrix (this phenomenon is also called exaggerated ECM production), thus induces scarring and organ failure. This makes it more difficult for oxygen to pass into bloodstreams in the lungs, and the thickened alveoli results in a weakened lung capacity.

While it's too early to establish long-term effects of the disease, several scans released by a Hong Kong hospital have revealed "patterns similar to frosted glass [in the patients’ lungs], suggesting there was organ damage” (Fig.1). What appears in these patients’ CT scans are "ground glass," a phenomenon in which fluid builds up in lungs and presents itself as white patches. 

The coronavirus pandemic is still in its heights, and frankly, there are not much that we can do about. However, it is no longer something that we can underestimate or underrate. Despite no evidence in proving its effects against the prevention of the coronavirus, masks can prevent droplet transmissions and therefore should be wore, at least in crowded and confined spaces. Wash hands and use alcohol disinfectants after handling public objects and before eating. Most importantly, keep yourself healthy no matter what. 

Fig.1 CT scans of patients reveal the accumulation of fluids in lungs after the SARS-CoV-2 infection

Reference:

“False Claim: Doctors Offer Advice for Preventing COVID-19, Symptoms like Coughing and Fever Indicate Pulmonary Fibrosis, Fibrosis Is Detectable by Holding Your Breath for 10 Seconds, Drinking Water Every 15 Minutes Repels Coronavirus.” Reuters, Thomson Reuters, 17 Mar. 2020, www.reuters.com/article/uk-factcheck-covid-advice-self-test-drin/false-claim-doctors-offer-advice-for-preventing-covid-19-symptoms-like-coughing-and-fever-indicate-pulmonary-fibrosis-fibrosis-is-detectable-by-holding-your-breath-for-10-seconds-drinking-water-every-15-minutes-repels-coronavirus-idUSKBN2142B6.

Bostock, Bill. “Those Who Recover From Coronavirus Can Be Left With Reduced Lung Function, Say Doctors.” ScienceAlert, 14 Mar. 2020, www.sciencealert.com/even-those-who-recover-from-corona-can-be-left-gasping-for-breath-afterwards.

G M-K Tse, K-F To, et al. Pulmonary pathological features in coronavirus associated severe acute respiratory syndrome (SARS). NCBI, 2004.

Ryan T. Kendall, Carol A. Feghali-Bostwick. Fibroblasts in fibrosis: novel roles and mediators. NCBI, 2014.

Motor Proteins: Cytoskeleton Filament Motor Proteins

Motor proteins are proteins that transform chemical energy into mechanical work. They are divided into three categories: cytoskeleton filaments motor proteins, nucleic acid motor proteins, and rotary motor proteins. In this article, we will talk in-depth about cytoskeleton filament motor proteins.

Cytoskeleton filament motor protein

Cytoskeleton filament motor proteins are motor proteins that associate and move along cytoskeleton filaments. This includes myosins, kinesins, and dyneins.

Myosin

Myosins are motor proteins that move along microfilaments; thus, they are also called actin motor proteins (because they interact with the actin of microfilaments). Myosins hydrolyze ATP as the source of energy and use it to propel their movements toward the plus end of an actin filament.

There are as many as 18 types of myosins that are known. Myosin II, for instance, is responsible for generating muscle contraction and dividing a cell during cytokinesis. Myosin V is involved in vesicle and organelle transport. Myosin XI is involved in cytoplasmic streaming, wherein movement along  microfilament networks in the cell allows organelles and cytoplasm to stream in a particular direction.

The movement of myosin is characterized by a release of actin during every cycle. What does this mean? Take muscle-contracting myosin II as an example. Myosin attaches to an actin component, moves once, and then dissociates from the actin. It then attaches again onto actin. This is the cycle of myosin movement.

Kinesin

Kinesins associate and move along microtubules, involving in the anterograde movement [1], which directs the transport of cargoes toward the plus end of microtubules. However, kinesins can also travel toward the minus-end, depending on whether the kinesin has an N-terminal or a C-terminal cargo-binding region. Anyway, just keep in mind the relationship between kinesin and anterograde transport.

Kinesins are primarily involved in the separation of chromosomes during cell division and also the shuttling of mitochondria, Golgi bodies, and vesicles within eukaryotic cells.

Unlike the movements of myosins, kinesins are rather highly processive. This means that kinesins move a great deal of “steps” before dissociating their carriages. Recall the shape of a kinesin [click]. The two heavy chains that attach to the microtubule function like legs, “walking” on the microtubule for a cycle of as much as hundreds of steps, while the two light chains attach to vesicles or organelles like hands.

Dynein

Dyneins move along microtubules through the retrograde movement. Dyneins are larger and more complex than kinesin and myosin motors, composing of two or three heavy chains and a large and variable number of associated light chains. Dyneins move toward the minus end of microtubules, where the nucleus locates.

There are mainly two types of dyneins. Axonemal dyneins facilitate the beating of cilia and flagella by sliding microtubules. Cytoplasmic dyneins facilitate the transport of intracellular cargos. 15 types of axonemal dynein are presently discovered, but only two cytoplasmic forms are known.

Summary

Myosin – microfilament - muscle contraction - cytokinesis (microfilament)

Kinesin – microtubule - anterograde - separation of chromosome - transport

Dynein – microtubule – retrograde - beating of flagella and cilia - transport

Reference:

Lodish H, Berk A, Zipursky SL, et al. Molecular Cell Biology, 4th edition. W. H. Freeman, 2000.

Berg JM, Tymoczko JL, Stryer L. Biochemistry, 5th edition. W. H. Freeman, 2002.

Anatoly B. Kolomeisky. Motor Proteins and Molecular Motors: How to Operate Machines at Nanoscale. NCBI, 2013.

Cytoskeleton: Microfilament, Intermediate Filament, and Microtubule

The cytoskeleton is a network of fibers that extends throughout the cytoplasm and aids the structures and activities of a cell. It is responsible for maintaining the shape of a cell, anchoring organelles and vesicles, assisting intracellular transport, and manipulating the plasma membrane to form food vacuoles and phagocytic vesicles. In this article, we will differentiate the three kinds of cytoskeletons- microtubule, microfilament, and intermediate filament- and make a clear comparison between them.

Microtubule

Microtubules are hollow fibers composed of a single type of globular (round) protein, called tubulin. Tubulin is a dimer formed by two closely related polypeptides, α-tubulin and β-tubulin, and it polymerizes (connects together) to form microtubules.

Microtubule is a polar structure, which is important because polarity gives molecules directionality, and microtubule uses this property to direct its movements as it rapidly assembles and disassembles to a certain direction in the cell. The specific mechanism regarding microtubule’s extension and shrinkage is rather complicated, however, and it will be mentioned in another article (Microtubule and Dynamic Instability).

Microtubule plays a very important role in many cellular processes. It forms the structural support of a cell with microfilament and intermediate filament. It also makes up the internal structure of cilia and flagella, in a “9+2” arrangement [click to understand more]. It provides a platform for intracellular transport and is also involved in the formation of spindles and the separation of eukaryotic chromosomes during cell division (mitosis and meiosis).

Microfilament

Microfilaments are thin solid rods composed of globular proteins called actin. Actin subunits form a twisted double chain that results in the shape of a microfilament. Microfilaments, like microtubules, are polar molecules.

Microfilament networks are found just inside the plasma membrane (cortical microfilament) of cells, stabilizing the outer cytoplasmic layer (cortex) of the cell. This is also the reason why cells can form pseudopodia or conduct phagocytic activities. Microfilaments also interact with motor proteins called myosin that bring about the contraction of muscle cells.

Intermediate filament

Intermediate filaments are composed of a variety of proteins, differing from the single-polymer microtubule and microfilament. The type of protein that polymerizes into intermediate filament depends on different cell types, but they share a common structural organization (meaning that they are constructed based on the same principle). Intermediate filaments only provide structural support in a cell.

Intermediate filaments are apolar, meaning that they do not have distinct plus and minus ends like microtubules and microfilaments do. Thus, they are assembled end to end (sort of like DNAs) and both ends are equivalent.

Here are some examples of intermediate filaments to give you a better picture:

• Types I and II intermediate filaments consist of two groups of keratins that are responsible for the production of hair, nails, and horns.
• Type IV intermediate filament proteins include three neurofilament (NF) proteins that support the structures of long, thin axons.
•  Type V intermediate filament proteins are the nuclear lamins, which are components of the nuclear envelope, holding the nucleus in place.

Structural support

Microtubules, along with intermediate filament and microfilament, provide a cell’s structural support. Microtubules, being hollow tubes, act as girders (橫樑) that resist compression and maintain a cell’s dome shape. Microfilaments, which are solid rods, bear tensions exerted on the cell (hold the cell’s shape so the cell would not stretch when being pulled by a force). It is also responsible for the change in cell shape (phagocytosis, etc.). The job of intermediate filaments is to reinforce the shape of a cell and fix the position of certain organelles. Unlike microtubule and microfilament, which assembles and disassembles, the intermediate filament is often fixed in position, so it secures the structure of the cell and keeps organelles such as the nucleus in place.

An overview of the organization of microtubules and microfilaments in an animal cell. Intermediate filaments are not indicated, but keep in mind that they provide structural support for the cell, so their organization should be close to that of microtubules.

The general building of microtubules and microfilaments. Intermediate filaments are not shown, because they varied in composition. However, their structures as solid rods are similar to that of micofilaments. 

Reference:

Campbell, et al. Biology: A Global Approach. 11th ed., Pearson, 2017.

Cooper GM. The Cell: A Molecular Approach. 2nd ed., 2000.

Lodish H, Berk A, Zipursky SL, et al. Molecular Cell Biology. 4th ed., W. H. Freeman, 2000.

Asexual and Sexual Reproduction

Animals can reproduce by means of asexual or sexual reproduction that best suit their population, the environment, or other prerequisites. In this article, we will discuss the different mechanisms regarding the asexual and sexual reproduction of invertebrates and vertebrates.

Mechanisms of asexual reproduction

Invertebrates carry out the several simplest forms of asexual reproduction.

Budding: new individuals arise from the outgrowth of existing ones; in any case of budding, you can observe the trait “connected individuals,” because the offspring and parents are connected together.

Fission: the splitting and separation of a parent organism into two individuals of about the same size; e.g. binary fission in bacteria.

Fragmentation and regeneration: as the name confirms, this type of reproduction is a two-step process; appears in annelids, sponges, corals, cnidarians, and tunicates.

Parthenogenesis: happens when an egg develops without being fertilized; it can be observed in both invertebrates and vertebrate (much rare). Among invertebrates, this can occur in species of bees, wasps, and ants. Male bees, for instance, are fertile haploid adults that are not fertilized, while female bees are fertile diploid adults. Among vertebrates, such as the Komodo dragon and hammerhead shark, females can produce genetically-identical offspring as a rare response to low population density.

Variations of sexual reproduction

Normally, among vertebrates, as in humans, sexual reproduction involves simply the mating between a male and a female individual. However, for many sexual animals, finding a mate can be difficult, and this is the reason for the emergence of deviations of sexual reproduction.

Hermaphroditism: characterized by an individual having both the male and female reproductive system; this type of adaption makes the finding of a mate easier in some vertebrates (any two individuals can mate).Sometimes, self-fertilization is possible.

Sex reversal: individuals can transform between male and female; this is especially useful for sedentary animals like oysters and corals, because by transforming into males during the time of ovulation, more gametes (sperm) is released into the environment so chances of fertilization can greatly increase.

Parthenogenesis of bees.

Reference:

Campbell, et al. Biology: A Global Approach. 11th ed., Pearson, 2017.

Axonal Transport

Recall that in neurons, peptide transmitters such as glycine and GABA are synthesized in the neuron cell body, packaged in vesicles, and then transported to nerve terminals. But how is this process carried out? In this article, you will learn the specifics of axonal transport, which is responsible for the transport of substances across a neuron.

Preface

Axonal transport relies on microtubules that run along the neural axon and serve as ‘tracks’ for motor proteins like kinesin and dynein. They are capable of binding to and transporting mitochondria, cytoskeletal polymers, and synaptic vesicles containing neurotransmitters. Axonal transport is categorized by fast or slow, anterograde (away from the cell body) or retrograde (to the cell body).

Fast and slow transport

Motor proteins carrying vesicular cargoes move relatively fast compare with those transporting cytoskeletal proteins or organelles such as mitochondria.

Through fluorescence microscopy, it is discovered that slow transport is not indeed slower than fast transport. Instead, slow transport processes with a mechanism called "Stop and Go," in which motor proteins constantly pauses during the transport, making the overall transit rate much slower.

Anterograde transport

Anterograde transport moves molecules/organelles outward from the cell body to the axonal terminal or cell membrane. Kinesin is responsible for both the fast and slow transport of cargo during an anterograde transport. It is good to remember that kinesin is an ATPase and is also involved in the separation of chromosomes during mitosis and meiosis. Lipids, proteins, and substances packed in vesicles that cannot be synthesized in the axon or the axonal terminal, as well as organelles like mitochondria, uses anterograde transport to travel across the neuron.

Retrograde transport

Retrograde transport, on the other hand, carries molecules/organelles away from the axonal terminal towards the cell body. Utilizing dynein as the motor protein, retrograde transport returns used synaptic vesicles, deteriorated organelles, and carries signals from the synapse back to the cell body.

A view of axonal transport.

Reference:

Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2^nd ed., 2001.

Summary of Neurotransmitters

Neurotransmitters are molecules responsible for the carrying of messages (signals) between neurons. It involves various areas, including biology, psychology, and chemistry, making it an especially crucial topic. Today, we will discuss the major neurotransmitters used by the human body and also their significances.

Acetylcholine

Acetylcholine is a transmitter used by all motor axons, autonomic preganglionic neurons, postganglionic parasympathetic fibers, and some cells of the motor cortex and basal ganglia. It is the chief neurotransmitter of the parasympathetic nervous system, which contracts smooth muscles, dilates blood vessels, increases bodily secretions, and slows the heart rate (vasodilator).

*preganglionic neurons connect the CNS to the ganglia (groups of neuron cell bodies in the peripheral nervous system), and postganglionic neurons connect the ganglia to the effector organ. The terms autonomic, parasympathetic, motor cortex (the region of the cerebral cortex involved with voluntary movements), and basal ganglia (a group of subcortical nuclei in the brains of vertebrates) will be discussed in later articles.

In the central nervous system, acetylcholine appears to have multiple roles, such as thought, memory, and learning; it is in abnormally short supply in the brains of persons with Alzheimer's disease.

Biogenic Amines

Biogenic amines include epinephrine, norepinephrine, dopamine, histamine, and serotonin. The first three belong to the category catecholamine (neurotransmitters containing the catechol, benzene with two side-by-side hydroxyl groups). Histamine and serotonin have otherwise composition.

The catecholamines are all derived from the amino acid tyrosine that is catalyzed by the enzyme tyrosine hydroxylase into DOPA. Information about this detailed process will be explained in another article regarding adrenergic transmission [click to understand more].

Dopamine is produced by the action of the enzyme DOPA carboxylase on DOPA. It is present in several brain regions. Dopamine coming from the substantia nigra into the corpus striatum represents the major dopamine activity, and it plays an essential role in the coordination of body movements. Dopamine is also believed to be involved in motivation, reward, and reinforcement.

In Parkinson's disease, the dopaminergic neurons of the substantia nigra degenerate, leading to characteristic motor dysfunction.

Norepinephrine is synthesized from dopamine by the enzyme dopamine β-hydroxylase. It is the primary transmitter for postganglionic sympathetic neurons, which is released into the blood from the adrenal medulla. In the brain, norepinephrine is synthesized by the locus coeruleus, a nucleus (cluster of neurons in the CNS) in the pon, where it influences sleep and wakefulness, attention, and feeding behavior.

Epinephrine is produced from norepinephrine by the enzyme phenylethanolamine-N-methyltransferase (PNMT). It is released by chromaffin cells (neuroendocrine cells) of the adrenal medulla and the rostral ventromedial medulla (RVM), a group of neurons in the medulla oblongata. Epinephrine plays an important role in the fight-or-flight response, as well as regulating visceral functions (e.g. respiration)

Histamine is present in neurons of the hypothalamus. In the brain, histamine mediates arousal and attention, similar to that of ACh and norepinephrine. It is also released from mast cells in response to allergic reactions or tissue damage.

Serotonin is found in high concentrations in the raphe region of the pons and upper brainstem and has a wide projection to the forebrain. It involves a wide range of behaviors, including sleep and wakefulness, cognition, the feeling of happiness, etc. (unnecessary to really know its specific effect)

Reuptake by the presynaptic membrane is a major factor in terminating transmitter action of the biogenic amines.

Amino Acids

Amino acids include glycine,y-aminobutyric acid (GABA), glutamate, and aspartate.

Glycine is an inhibitory transmitter in spinal interneurons. GABA is an inhibitory transmitter of the central nervous system. Both of them generate IPSPs via ligand-gated Cl- channels. Glycine is produced by the mitochondria, whereas GABA is synthesized from glutamate.

Glutamate and aspartate are excitatory transmitters of the CNS that generate EPSPs, and are products of the Krebs cycle. Both glutamate and aspartate are produced in the mitochondria

While non-peptide transmitters are synthesized in nerve terminals, peptide transmitters are synthesized in the neuron cell body, packaged in vesicles, and then transported to nerve terminals [click to understand more]. Both glutamate and aspartate are produced in the mitochondria

Reuptake by presynaptic membranes is a major factor terminating the transmitter action of the amino acids.

Nitric Oxide (NO)

Unlike other transmitters, NO is neither packaged in vesicles nor released by exocytosis. As a gas, it readily diffuses across cell membranes to adjacent target tissue once being synthesized. NO is an inhibitory transmitter in the central and enteric nervous systems. In smooth muscles, NO is responsible for vasodilation and increasing blood flow (endothelial-derived relaxing factor).

List of neurotransmitters and their locations.

Reference:

Robert B. Dunn. 2002. USMLE Step 1: Physiology Notes.

Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2^nd ed., 2001.

The Editors of Encyclopaedia Britannica. “Acetylcholine.” Encyclopædia Britannica, Encyclopædia Britannica, Inc., 26 Dec. 2019, www.britannica.com/science/acetylcholine.

The Human Excretory System

The excretory systems are central to homeostasis because they dispose of metabolic wastes and control body fluid composition through the regulation of solute movement between internal fluids and the external environment. Today we will overlook the basic structures of the human excretory system.

Excretory organs

Kidneys: a pair of organs that functions in both osmoregulation and excretion.

Ureter: the duct in which urine produced by each kidney exits and drains into the urinary bladder.

Urinary bladder: a sac where urine is collected from the ureters.

Urethra: the tube in which urine is expelled from the urinary bladder during urination; empties to the outside near the vagina in females and through the penis in males.

Sphincter muscles near the junction of the urethra and bladder regulate urination.

Kidney structure

Renal cortex: the granular outer section of a dissected kidney; contains the glomeruli and convoluted tubules of nephrons.

Renal medulla: the smooth, striated inner section of a dissected kidney; contains the loops of Henle and the collecting tubules of nephrons.

In both the renal cortex and medulla, blood is supplied by a renal artery and drained by a renal vein. Within them lie tightly packed excretory tubules and blood vessels. It is these tubules that carry out the process of filtration of blood entering the kidney. Fluids in the filtrate are reabsorbed into the surrounding blood vessels and exit the kidney in the renal vein.

Renal pelvis: an inner cavity formed by the ureter as it enters the kidney; urine collects into the pelvis from the collecting tubules and exits the kidney via the ureter.

Types of nephron

Nephrons: the functional units of a kidney; exist between and across the renal cortex and medulla.

Cortical nephrons: nephrons that only reach a short distance into the medulla; represents 85% of total nephrons in a human kidney.

Juxtamedullary nephrons: nephrons that extend deep into the medulla; are essential for the generation of concentrated urine (hyperosmotic) due to its long loop of Henle.

Nephron

Glomerulus: a ball of capillaries that is surrounded by the Bowman’s capsule; blood pressure forces fluid from the blood in the glomerulus into the lumen of the Bowman’s capsule.

Bowman’s capsule: a cup-shaped swelling at the end of tubule; passes filtrate collected from the glomerulus to the proximal tubule.

Proximal tubule: the section of the tubule in which reabsorption of ions, water, and nutrients takes place.

Loop of Henle: functionally divided into two sections, the descending limb and the ascending limb. The descending limb consists mainly of aquaporin and is responsible for the removal of water. The ascending limb is impermeable to water and further divided into two regions, the thin and thick segment. In the thin segment, NaCl diffuses out of the permeable tubule into the interstitial fluid, whereas in the thick segment NaCl is actively transported.

Distal tubule: plays a key role in regulating the K⁺ and NaCl concentration of body fluids, and contributes to the regulation of pH by controlling the secretion of H⁺ and reabsorption of HCO3^-.

Collecting duct: processes the filtrate into urine and carries it to the renal pelvis; hormonal control of the permeability of the collecting duct ultimately determines the concentration of the urine.

Blood enters the nephron through the afferent arteriole and leaves through the efferent arteriole. The capillaries of this arteriole form the branched peritubular capillaries, which surround the proximal and distal tubule. Other branches extend downward and form the vasa recta, surrounding the loop of Henle.

An overview of the human excretory system

Nephron organization

Reference:

Campbell, et al. Biology: A Global Approach. 11th ed., Pearson, 2017.

The Editors of Encyclopaedia Britannica. “Kidney.” Encyclopædia Britannica, Encyclopædia Britannica, Inc., 23 Jan. 2019, www.britannica.com/science/kidney#ref287943.

Supplements on the Action Potential

Conduction velocity is an important topic when considering an action potential because the rate at which the axons within nerves conduct action potentials governs how rapidly an animal can react to a certain stimulus. When studying through the information, make sure to connect the factors of conduction velocity with means of evolutionary adaption so you can get a better idea of the reason behind the structural differences of various types of neurons.

Conduction Velocity of the Action Potential

Main Factors:

Cell diameter: The greater the cell diameter, the greater the conduction velocity.

Myelin: The greater the myelination, the greater the conduction velocity

• Large myelinated fibers = fast conduction
• Small unmyelinated fibers = slow conduction

Myelin sheaths are produced by glia: oligodendrocytes in the CNS and Schwann cells in the PNS. They wrap many layers of lipid membranes that act as excellent insulators.

In myelinated axons, voltage-gated sodium channels are restricted to gaps in the myelin sheath called nodes of Ranvier, as well as the contact between the extracellular fluid and the axonal membrane. As a result, action potentials are not generated in the regions between the nodes; instead, the current generated by an action potential at a node travels within the axon all the way to the next node. This mechanism for propagating action potentials is called saltatory conduction. The action potential appears to be jumping from node to node along the axon.

The major selective advantage of myelination is its space efficiency. Recall that both cell diameter and myelination can increase the conduction velocity of an action potential. However, a myelinated axon 20 μm in diameter has a conduction speed faster than an unmyelinated axon of diameter 40 times greater. Hence, more myelinated axons can be packed into the space occupied by just one giant axon.

Propagation of action potentials in a myelinated axon

Reference: 

Campbell, et al. Biology: A Global Approach. 11th ed., Pearson, 2017.

Robert B. Dunn. 2002. USMLE Step 1: Physiology Notes.

Neuromuscular Transmission

Neuromuscular (Cholinergic) transmission is a type of synaptic transmission that occurs in the neuromuscular junction, the synapse between the axons of a motor neuron and a skeletal fiber. It relies on the binding of acetylcholine (ACh) released from presynaptic nerve terminals to acetylcholine receptors on the postsynaptic membrane. This process is very important because it enables a motor neuron to transmit a signal to the muscle fiber, causing muscle contraction.

Sequence:

1.      Action potential travels down the axon, ends in the presynaptic motor axon terminal, and opens voltage-gated calcium channels.

2.      Increase in Ca²⁺ permeability of the axon terminal causes an influx of extracellular Ca²⁺ into the axon terminal.

3.      The rise in intracellular free Ca²⁺causes the release of acetylcholine from synaptic vesicles into the synaptic cleft.

4.      Acetylcholine diffuses to the postjunctional membrane (represents a major time component).

5.      Acetylcholine binds to cholinergic receptors (ligand channels) on the postjunctional membrane, leading to the opening of the channels. The channels will remain open until the acetylcholine is removed.

6.      Opening of ligand-dependent channels results in an increased conductance to Na⁺ and K⁺. Because of the greater net force on sodium, an influx of sodium dominates.

7.      Influx of Na⁺ causes local depolarization of the postjunctional membrane. This depolarization is referred to as the end-plate potential (or EPP). The more acetylcholine that is released, the greater the depolarization (the greater the end-plate potential). Because the skeletal muscle membrane in the synaptic region does not have voltage-gated sodium channels, the action potential cannot be initiated in this region.

8.      The EPP spreads, causing depolarization of areas of muscle membrane adjacent to the end plate, where voltage-gated sodium channels are present. Their opening causes the initiation of an action potential that spreads across the surface of the skeletal muscle cell.

Single quanta of acetylcholine are released randomly under resting conditions. Each produces a small depolarization of the postsynaptic membrane, called a miniature end-plate potential (MEPP). MEPPs do not generate action potentials.

Neuromuscular transmission

Acetylcholine synthesis and choline recycling

Acetylcholine is an acetyl ester of choline. Its synthesis takes place in the cytoplasm and is catalyzed by choline acetyltransferase. Acetylcholine is then taken up into synaptic vesicles by an active vesicular transport mechanism. Acetylcholinesterase, which is weakly associated with the postsynaptic membrane and is located within the synaptic cleft, terminates the action of the transmitter via hydrolysis to acetate and choline. The active reuptake of choline from the extracellular fluid into the nerve terminal recycles the choline.

Acetylcholine synthesis and choline recycling

Reference:

Robert B. Dunn. 2002. USMLE Step 1: Physiology Notes.

Water

Water is the molecule that sustains all kinds of life forms. Its structure allows it to interact with other molecules and water molecules itself, resulting in many unique emergent properties that help make Earth suitable for life.

Polar covalent bond

Water is a polar molecule, meaning that its overall charge is unevenly distributed. In an H₂O molecule, the oxygen has two regions of partial negative charge (δ⁻) and the hydrogen has a partial positive charge (δ⁺) due to the difference in electronegativity between the two elements. Oxygen is more electronegative than hydrogen, so the electrons of the covalent bonds spend more time closer to oxygen than to hydrogen, leading to the formation of polar covalent bonds as a result in the unequal sharing of electrons.

The partial charges of water molecules make it possible for it to form hydrogen bonds with one another, through intermolecular interaction between the hydrogen of one molecule and the oxygen of another. Hydrogen bonds, as you will later see, contribute to a variety of important properties in which water possesses.

Cohesive behavior

Hydrogen bonds hold water molecules together, making it more structured than most other liquids. Several phenomena arise as a result of this behavior, such as cohesion, adhesion, and surface tension.

Cohesion: the attraction between different substances through hydrogen bonds, in this case, water molecules and other substances. Think of a straw. Without cohesion, you would not be able to suck up any water because the water molecules are unable to cling onto the surface of the straw. This is cohesion.

Adhesion: the clinging of one substance to another, in this case, water molecules to water molecules. Let’s take the straw as an example again. Without adhesion, you would again be unable to suck up any water, because the water will fall down the straw due to gravity since the molecules below are not attached to the ones above.

Surface tension: a measure of how difficult it is to stretch or break the surface of a liquid. Water has an unusually high surface tension due to its hydrogen bonding, and this can be observed in a water droplet, which has the shape of a dome.

Moderation of temperature

Water moderates air temperature by absorbing heat from the air that is warmer and releasing the stored heat to air that is cooler. Several characteristics of water allow it to do so effectively, and that is its unusually high specific heat and heat of vaporization.

Specific heat: defined as the amount of heat that must be absorbed or lost for 1 g of a substance to change its temperature by 1°C. The specific number and calculations of water’s specific heat (1 cal/g．°C) is of little importance here, and you only need to know that compared with most other substances, water has an unusually high specific heat, making it less likely to change temperature than other liquids when absorbing or losing a given amount of heat. This is due to its hydrogen bonds: a lot of heat are spend on disrupting water’s hydrogen bonds before the water molecules can begin moving faster, and when the temperature drops slightly, many additional hydrogen bonds are formed, releasing heat into its surroundings.

The heat of vaporization: the quantity of heat a liquid must absorb for 1 g of it to be converted from liquid to gas. For the same reason, that water has a high specific heat, it also has a high heat of vaporization relative to other liquids. This characteristic of water allows it to moderate Earth’s climate, through evaporative cooling and circulation of air currents across the globe.

Ice v. liquid water

Water is one of the few substances that are less dense as a solid than as a liquid. In other words, ice floats on liquid water. Water expands when solidify because its hydrogen bonds form crystalline lattices when freezing, making ice about 10% less dense than liquid water, at 4 °C. This property has many values, including the sustentation of polar ice caps and its ecosystems.

Water as a solvent

Water is a very versatile solvent, due to its characteristic of being a polar molecule. The partial charges of water molecules, both positive and negative, can surround solute ions and form a sphere of water molecules called the hydration shell. That is, a compound is identified as “water-soluble” as long as water is able to establish a hydration shell around it. This characteristic is very vital since many different kinds of polar compounds are dissolved in the water of such biological fluids like blood, the sap of plants, and the liquid within all cells.

Water as a polar molecule

Reference: 

Campbell, et al. Biology: A Global Approach. 11th ed., Pearson, 2017.

Action Potential

When a neuron responds to a stimulus, a sudden change in the voltage (stimulated by the stimulus) across the dendrites and the cell body causes specialized channels called voltage-gated ion channels to open on the surface of axons, triggering an action potential.

An action potential is defined as a rapid membrane depolarization that changes the normal resting negative potential to a positive potential follow by a repolarization back to the normal negative membrane potential.

Involved Membrane Channels

Ungated potassium channel: always open; maintains K⁺ efflux

Voltage-gated sodium channel: closed under resting conditions, quickly opens and closes when detecting nearby membrane depolarization; once closes, will not respond to a second stimulus until the cell almost completely repolarizes. This channel is required for the depolarization phase (influx of Na⁺) of an action potential, and preventing the opening of these channels, which halts depolarization, will prevent the development of an action potential.

Voltage-gated potassium channel: As is the case for the voltage-gated sodium channel, membrane depolarization is the signal that causes it to open. However, it opens more slowly than the sodium channel, and thus its opening peaks later during the action potential. It provides a rapid repolarization phase, so preventing its opening slows repolarization.

Threshold and Subthreshold

When the neuron is depolarized to a level called the threshold, it fires an action potential. Subthreshold potentials of all types are referred to as electrotonic potentials (graded potentials).

Subthreshold potential v. Action potential:

Proportional to stimulus strength (graded) │   independent of stimulus strength (all or none)

Not propagated but decremental with distance │   propagated unchanged in magnitude

Exhibits summation │   summation not possible

Depolarization phase

Initial depolarization: voltage-gated sodium channels open (opens fast, close fast). Membrane conductance to sodium increases, rapid Na⁺ influx, depolarizing the membrane close to the sodium equilibrium potential (+65 mV).

Sodium channels are opening throughout depolarization, and peak sodium conductance is not reached until just before the peak of the action potential. Even though peak sodium conductance represents a situation with a large number of open sodium channels, influx is minimal because the membrane potential is close to the sodium ion equilibrium potential (low electric force; mentioned in Resting Potential).

Repolarization phase

Early repolarization: the voltage-gated sodium channels rapidly close, eliminating Na⁺ influx. Meanwhile, the voltage-gated potassium channels are still opening (they are slower, remember?), increasing potassium conductance beyond the value under resting conditions. This leads to rapid potassium ion efflux that repolarizes the cell.

Peak potassium conductance does not occur until about mid-repolarization. At this point, even though the force on the potassium ions is less than at the beginning of repolarization, there is greater efflux because of the much greater conductance. If the voltage-gated potassium channels do not open during repolarization, the cell will still repolarize through the ungated potassium channels. However, the process will be slower.

The original gradients are reestablished via the Na/K-ATPase pump.

Refractory periods

Absolute refractory period: during this period, no matter how strong the stimulus is, a second action potential cannot be induced. Therefore, its length determines the maximum frequency of action potentials.

Relative refractory period: during this period, a greater than normal stimulus is required to induce a second action potential.

Breakdown of an action potential.

Axon Action Potential and Changes in Conductance

Reference:

Campbell, et al. Biology: A Global Approach. 11th ed., Pearson, 2017.

Robert B. Dunn. 2002. USMLE Step 1: Physiology Notes.