7.1:
Neuromuscular Junction And Blockade
The neuromuscular junction, or NMJ, is a site of chemical communication between a motor neuron and muscle fiber to facilitate skeletal muscle contraction. Drugs called neuromuscular blockers target the NMJ and help induce muscle paralysis.
The NMJ consists of the motor nerve terminal and a muscle fiber's motor end plate separated by a small synaptic cleft. Acetylcholine, a neurotransmitter released from the nerve terminal, acts as a chemical messenger between the two cells.
When an action potential reaches the neuronal end, it triggers the release of acetylcholine into the synaptic cleft. Acetylcholine binds to the nicotinic receptors on the motor endplate and opens ion channels to allow sodium ions into the cell.
The influx of sodium ions depolarizes the muscle membrane, propagating the action potential and causing muscle contraction.
Because of their structural similarity with acetylcholine, neuromuscular blockers can bind to the nicotinic receptors and block impulse transmission.
For example, succinylcholine competes with acetylcholine to bind the receptors and inhibit its action. Such neuromuscular blockade makes the muscles relax in sedated patients during surgery.
7.1:
Neuromuscular Junction And Blockade
The site of chemical communication between a motor neuron and a muscle fiber is called the neuromuscular junction (NMJ). The end of the motor neuron at the NMJ divides into a cluster of synaptic end bulbs. The cytoplasm of these bulbs consists of synaptic vesicles enclosing acetylcholine molecules, the principal neurotransmitter released at the NMJ. The region opposite the synaptic bulb that ends in the muscle fiber is called the motor end plate, which has acetylcholine receptors. Within the NMJ, action potential arises, and impulse transmission across the NMJ facilitates skeletal muscle contractions.
As the nerve impulse arrives at the synaptic bulb ends, it stimulates Ca2+ influx by opening the calcium channels, which stimulates exocytosis of the synaptic vesicles and release of acetylcholine in the synaptic cleft. Two acetylcholine molecules bind to the receptor at the motor end plate, opening Na+ channels. Na+ influx inside the muscle fiber changes the membrane potential, triggering a muscle action potential followed by muscle contraction. The effect of acetylcholine is brief as the enzyme acetylcholinesterase breaks down acetylcholine into choline and acetate.
Certain agents can block the events at the NMJ to prevent muscle contraction. Botulinum toxin prevents exocytosis of the synaptic vesicles, preventing acetylcholine release. Tubocurarine and other neuromuscular blockers can limit impulse transmission across the NMJ by binding to acetylcholine receptors. This is important for treating several pathological conditions and for use during patient surgeries to induce muscle relaxation and temporary paralysis.