Sequence of transmission at the neuromuscular junction

* The neuronal action potential arrives at the synaptic terminal of the motor neuron nerve fibre. Depolarisation of the synaptic terminal occurs. Opening of voltage-gated calcium channels leads to an increase in intracellular calcium concentration.

* Acetylcholine is released by a process of vesicular exocytosis from membrane-bound synaptic vesicles in axon terminals into the junctional cleft (10-20 nm width). Each vesicle contains about 10 000 molecules of the neurotransmitter -accounting for quantal release in multi-molecular packets or quanta in the absence of presynaptic electrical activity. This coupling of depolarisation and neurotransmitter release is caused by the influx of calcium ions.

* Diffusion of acetylcholine occurs down a concentration gradient towards the motor end-plate, which contains ligand-gated, nicotinic acetylcholine receptors.

* Acetylcholine interacts with postsynaptic or postjunctional acetylcholine receptors. The chemical signal (binding of two acetylcholine molecules) is converted into electric signals (i.e. a transient permeability change and depolarisation in the postsynaptic membrane). Denervation hypersensitivity in skeletal muscle is due to the increased expression of nicotinic cholinergic receptors and their spread to regions away from the motor end-plate.

* Depolarisation of the motor end-plate produces an end-plate potential. When the end-plate potential exceeds a threshold potential of excitability, an action potential is triggered.

* The action potential passes into the T-tubules and causes depolarisation with opening of voltage-gated calcium channels of the sarcoplasmic reticulum.

Acetylcholine Junction

Membrane

Figure 9.3 Neuromuscular junction. Ach, acetylcholine; EPSP, excitatory postsynaptic potential.

Membrane

Figure 9.3 Neuromuscular junction. Ach, acetylcholine; EPSP, excitatory postsynaptic potential.

* Dissociation of the acetylcholine/receptor complex occurs.

* Acetylcholine is hydrolysed by acetylcholinesterase. Reuptake of choline back into the nerve terminal ensues. Re-synthesis of acetylcholine follows, with storage in the synaptic vesicles.

The synaptic potential at the neuromuscular synapse was first studied in detail in the 1950s by Paul Fatt and Bernard Katz. Using curare they reduced the amplitude of the synaptic potential below the threshold for the action potential, thus isolating the synaptic potential in intracellular voltage recordings.

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