The process by which an action potential in a motoneurone initiates the contraction of all the muscle fibres that it innervates is referred to as neuromuscular transmission and involves a number of distinct stages:
1. The action potential arrives at the end of the axon of the motoneurone and triggers the opening of the voltage-gated Ca2+ channels in the axon terminal.
2. Ca2+ flows down its concentration gradient from the extracellular fluid into the axon terminal. Ca2+ then binds to proteins that enable synaptic vesicles to fuse with the neuronal plasma membrane, which subsequently results in the exocytosis of acetylcholine into the synaptic cleft which separates the axon terminal and the motor end plate.
3. Acetylcholine then diffuses across the cleft and binds to the nicotinic acetylcholine receptors in the folds on the sarcolemma.
4. The binding of acetylcholine to these receptors causes a depolarising graded potential in the muscle fibre which is known as the end-plate potential. The reason for this is that the binding of acetylcholine to this receptor triggers the opening of a relatively non-selective cation channel. This allows Na+ to flow into the cell and K+ out of the cell along their respective concentration gradients. However, the differences in electrochemical gradients that exists at the time of channel opening results in more Na+ flowing into the cell than K+ leaving the cell and so the overall effect is a net positive charge entering the cell and hence depolarisation.
5. In most instances the magnitude of the endplate potential is 3-4 times greater than that required to reach the action potential threshold for the muscle fibre. Consequently in almost every instance, an action potential in the motoneurone produces an action potential in the muscle fibres it innervates.
The effect of acetylcholine at the neuromuscular junction is limited by two mechanisms. The first mechanism is simply the diffusion of acetylcholine away from the endplate. The second mechanism involves the degradation of acetylcholine by the acetylcholinesterases found in the cleft.
Note that in most respects the mechanism of neuromuscular transmission is very similar to that of an excitatory postsynaptic potential. However, the magnitude of the end plate potential is much greater than that of an excitatory postsynaptic potential because acetylcholine is released over a larger surface area, and binds to many more receptors, thereby opening many more ion channels. Therefore, one end plate potential is generally more than sufficient to depolarise the sarcolemma to its threshold potential, which results in an action potential.
Most neuromuscular junctions are located near the middle of muscle fibres. Newly generated action potentials produce local ion currents that depolarise adjacent regions, producing more actional potentials at the next site, and so on, to cause action potential propagation. Action potentials propogate from neuromuscular junctions across the surface of the muscle fibre in both directions towards the end of the fibre and throughout the T-tubule network. Note that inhibitory postsynaptic potentials do not occur in human skeletal muscle. All neuromuscular junctions are excitatory