Biology101: 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.