2020年2月13日 星期四

Resting Potential


In neurons, as in other cells, ions are unequally distributed between the interior of cells and the surrounding fluid, resulting in a negatively charged environment in the cell relative to the outside. For a resting neuron, the resting potential is about -70 millivolts (mV).

Involved Membrane Channels


Potassium ions (K+) and sodium ions (Na+) play an essential role in the formation of the resting potential. During a resting potential, the concentration of K+ is higher inside the cell, while the concentration of Na+ is higher outside. This concentration gradient is well-established by important membrane channels.

Sodium-potassium pump: maintain the Na+ and K+ gradients; uses the energy of ATP hydrolysis to actively transport Na+ out of the cell and K+ into the cell, in a ratio of three to two, respectively. The pump acts slowly, producing a small net charge, so a neuron relies on ion channels to create a drastic gradient.

Potassium channel: also called the potassium leak channels, these channels permanently open and are crucial to the establishing of a resting potential. A neuron has many potassium channels, so the large efflux (outflow) of K+results in a negatively charged environment inside the cell.

Sodium channel: also called the sodium leak channels, these channels are also permanently open, just like the potassium channels. However, there is way less sodium channels than there are potassium channels, so Na+ cannot readily pass through the membrane, resulting in a positively charged environment outside the cell.

Electrochemical Equilibrium


Two vectors determine the state of equilibrium of a neuron-the concentration force and the electrical force. When both vectors are in balance, the neuron is said to be in equilibrium. Considering an electrochemical equilibrium requires imagination and logic; when dealing with questions of cells whose ions are not in equilibrium, keep in mind that you should deal each ion separately, balancing one force before considering the other.

When a neuron reaches equilibrium, you can try using the Nernst equation to calculate the equilibrium potential of individual ions.

                            [ion]outside   
Eion = 62 mV( log ――  )

                       [ion]inside


For instance, plugging the K+ concentration (extracellular concentration: 5 mM, intracellular concentration: 140 mM) into the Nernst equation reveals that the equilibrium potential for K+ is -90 mV, and Na+ (extracellular concentration: 150 mM, intracellular concentration: 15 mM) is +62 mV.

Because neither K+ nor Na+ is at equilibrium in a resting neuron, there is a net flow of each ion across the membrane. As long as the resting potential remains, the K+ and Na+ current, as well as the
ion concentrations, will hold steady, until an action potential is induced. And that will be another story to begin with.


Membrane channels and pumps generate the resting potential.


Reference:

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

2020年2月12日 星期三

Vertebrate Innate Immunity


In animals, there are two types of immunity: innate immunity is common among all animals, and adaptive immunity is found only in vertebrates. Innate immunity offers a primary defense in all animals and sets the stage for adaptive immunity in vertebrates.

Innate immunity includes barrier defenses and molecular recognition that relies on a small set of receptor proteins that bind to molecules or structures that are absent from animal bodies but common to a group of viruses, bacteria, or other pathogens.

Barrier Defense


Mammals have mucous membranes and skin as their barrier defenses. The mucous membranes line the respiratory, digestive, urinary, and reproductive tracts, producing mucus, a viscous fluid that traps pathogens and other particles. In airways, ciliated epithelial cells sweep mucus and entrapped material upward, preventing infection in the lungs. Saliva, tears, and mucous secretions which contain lysozyme bathe various exposed epithelia, wash away intruding bacteria and fungi, and destroys the cell walls of susceptible bacteria. The gastric juice (pH 2) as well as skin secretions such as oil and sweat (pH 3-5) also help prevents the growth of many bacteria.

Cellular Innate Defense


Mammals rely on recognition protein called Toll-like receptor (TLR) to detect, devour, and destroy invading pathogens. Each TLR protein binds to fragments of molecules characteristic of a set of pathogens. Upon recognizing the pathogen, TLR proteins produce signals that initiate responses tuned to the invading microorganism.

The two main types of phagocytic cells in the mammalian body are neutrophils and macrophages.

Neutrophils: circulate in the blood, get attracted by signals from infected tissues and then engulf and destroy the infecting pathogen.

Macrophages: larger phagocytic cells; migrate throughout the body or reside permanently in organs and tissues where they are likely to encounter pathogens, engulf, then destroy or present antigens.

Some other notable cells that are involved in innate defense include dendritic cells, eosinophils, and natural killer cells.

Dendritic cells: mainly populate tissues that contact the environment, such as skin; like macrophages, they are antigen-presenting cells (APC), engulfing pathogens and presenting the antigens.

Eosinophils: often found in tissues underlying an epithelium; defend against multicellular invaders such as parasitic worms by discharging destructive enzymes.

Natural killer cells: circulate throughout the body, detect the abnormal array of surface proteins characteristic of some virus-infected and cancerous cells, and release chemicals that lead to cell death.

Peptide and Protein Production


Pathogen recognition triggers the production and release of a variety of peptides and proteins that attack pathogens or impede their reproduction.

Antimicrobial peptides: damages broad groups of pathogens by disrupting membrane integrity.

Interferons: proteins that provide innate defense by interfering with viral infections; can be secreted by virus-infected cells to limit cell-to-cell infection, or secreted by some white blood cells to help activate macrophages.

Complement system: consists of roughly 30 proteins in blood plasma; circulate in an inactive state and are activated by substances on the surface of many pathogens, leads to lysis of invading cells.

Inflammatory Response


Characterized by 1. rubor (redness), 2. calor (heat), 3. tumor (swelling), 4. dolor (pain), and 5. function laesa (loss of function).
It is a set of events triggered by signaling molecules released upon injury or infection.

Step1: Activated macrophages discharge cytokines, signaling molecules that recruit neutrophils to the site of injury or infection. At the same time, mast cells, immune cells found in connective tissues, release the signaling molecule histamine at sites of damage.

Step2: Local blood supply increases, capillaries widen and become more permeable, allowing the delivery of antimicrobial peptides to the site. Activated complement proteins promote further release of histamine, attracting more phagocytic cells. Pus, a fluid rich in white blood cells, dead pathogens, and debris from damaged tissue, accumulates.

Step3: Phagocytic cells such as neutrophils digest pathogens and cell debris at the site and the tissue heals.

The three basic inflammations:
Local Inflammation
Systemic Inflammation (throughout the body)
Chronic Inflammation (ongoing)

Toll-like Receptor (TLR)

Antigen-Presenting Cells (APC)



Reference:

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

2020年2月11日 星期二

The Anatomy of a Neuron



Although the morphology of various types of neurons differs in some respects, they all contain four distinct regions with differing functions: the cell body, the dendrites, the axon, and the axon terminals. 

Cell Body


The cell body, or soma, contains the nucleus and is the site of the synthesis of virtually all neuronal proteins and membranes. Some proteins are synthesized in dendrites, but no proteins are made in axons and axon terminals, which do not contain ribosomes. Proteins and membranes that are required for renewal of the axon and nerve termini are synthesized in the cell body and assembled there into membranous vesicles or multiprotein particles by a process called anterograde transport. Transported along microtubules down the length of the axon to the terminals, these vesicles are inserted into the plasma membrane or other organelles. Axonal microtubules are also the tracks along which damaged membranes and organelles move up the axon toward the cell body; this process is called retrograde transport [1]. Lysosomes, where such material is degraded, are found only in the cell body.

In the CNS, neurons have extremely long dendrites with complex branches. This allows them to form synapses with and receive signals from a large number of other neurons. 
On the other hand, motor neurons and sensory neurons have long axons that can relay signals to and from the CNS.

Dendrite


Most neurons have multiple dendrites, which extend outward from the cell body and are specialized to receive chemical signals from the axon termini of other neurons. Dendrites convert these signals into small electric impulses and transmit them in the direction of the cell body. 

Axon


Almost every neuron has a single axon. Axons are specialized for the conduction of action potential away from the cell body toward the axon terminus generated as a result of a sudden change in voltage. In a typical neuron, the action potential duration is about a millisecond; when an action potential is not triggered, a neuron is in a resting state. 

Axon Terminal


An action potential is actively conducted down the axon into the axon terminals, small branches of the axon that form the synapses, or connections, with other cells.

Axon Hillock


Axon hillock is the junction (joining) of the cell body and the axon. It is also the site where an action potential originates.

Myelin Sheath


Myelin is a lipid-rich (fatty) substance that surrounds the axons of some nerve cells that act as insulation to increase the rate at which signals/information (encoded as electrical impulses) is passed along the axon. The myelin membranes originate from and are a part of the Schwann cells in the PNS and the oligodendroglial cells in the CNS. 


General Features of a Neuron





Reference: 

Overview of Neuron Structure and FunctionKhan Academy, https://www.khanacademy.org/science/biology/human-biology/neuron-nervous-system/a/overview-of-neuron-structure-and-function. Accessed 10 Jan. 2020.
Section 21.1 Overview of Neuron Structure and Function. Molecular Cell Biology. 4th Edition, NCBI, https://www.ncbi.nlm.nih.gov/books/NBK21535/. Accessed 10 Jan. 2020.
Campbell, et al. Biology: A Global Approach. 11th ed., Pearson, 2017.