Neuromuscular transmission: ion flow
Basic, Organ-Based and Clinical Sciences, Special Problems or Issues in Anesthesiology
Transmission of signals from nerve to muscle occurs at the neuromuscular junction resulting in contraction of muscle. An action potential is transmitted to the NMJ as the result of depolarization of the nerve. This is a function of sodium influx through membrane sodium channels, which result in depolarization of the membrane potential from -90mV. At a membrane potential around 0mV, potassium channels open and sodium channels start to close with a resulting membrane potential of roughly +10mV. At the presynaptic nerve terminal, calcium ions also enter and are stored in the sarcoplasmic reticulum and mitochondria. The presynaptic (nerve) terminal also synthesizes acetylcholine and stores it in small vesicles. Acetylcholine is released spontaneously in the synaptic cleft in small amounts leading to miniature end plate potentials, which do not cause muscle contraction. The arrival of a threshold action potential, and the resulting calcium influx cause an accelerated release of acetylcholine that is dependent on the amount of calcium influx. The amount of calcium influx is largely a function of duration of action potential (i.e. longer action potential results in more calcium influx, which results in more ACh release).
Acetylcholine diffuses across the synaptic cleft and reaches the post-synaptic nicotinic acetylcholine receptors. When ACh binds to the two α subunits, the receptor undergoes a conformational change, the central pore opens, and sodium influx occurs resulting in a more positive charge in the immediate area. The acetylcholine immediately detaches from the receptor and is destroyed by the enzyme acetylcholinesterase, which is also present in the cleft. Each of these current pulses that occur is additive with others and summates to produce an end plate current that depolarizes the end plate membrane. Once this end plate potential reaches a critical threshold, an action potential is propagated away from the end plate and leads to activation of muscle fiber contraction.