Structure
Neuromuscular junction refers to the intimate contact of the nerve endings with the muscle fibre to which they innervate. Characteristics of the nerve and muscle fibre at and near the neuromuscular junction are as follows :-
[Include diagram of NMJ]
Terminal button. –
- The axon of a neuron supplying a skeletal muscle loses its myelin sheath and divides into several fine branches which end in small swellings (knobs) called terminal buttons or end feet which forms a neuromuscular junction at the centre of muscle fiber
- The nerve terminal or the so-called synaptic knob contains many vesicles (approximately 300,000) containing acetylcholine and mitochondria. The acetylcholine is synthesized by the mitochondria and is stored in the vesicles.
Presynaptic membrane
- This refers to the axonal membrane lining the terminal buttons of the nerve endings.
Synaptic cleft.-
- It is a 50-100 nm wide space between the presynaptic membrane and the postsynaptic membrane.
- It is filled by ECF with reticular fibres forming the matrix.
Postsynaptic membrane
- This is the name given to the muscle fiber membrane (sarcolemma) in the region of neuromuscular junction.
- The muscle membrane in this region is thickened and depressed to form the synaptic trough in which the terminal button fits and is called motor end plate.
- The postsynaptic membrane contains receptor sites for acetylcholine called the nicotinic receptors.
- The matrix of cleft contains enzyme cholinesterase which hydrolyses acetylcholine.
Transmission of Impulse at Neuromuscular Junction
Initiation and propagation of action potential in motor neuron's axon ⬇️ Arrival of impulse at nerve terminal (at synaptic button) ⬇️ Increased permeability of nerve terminal membrane to calcium ions ⬇️ Diffusion of calcium ions from extracellular fluid to the interior of fibre leading to entry of Calcium ions into the terminal ⬇️ Release of acetylcholine from the nerve terminal ⬇️ Binding of acetylcholine to the end plate acetylcholine receptors present in muscle membrane ⬇️ Opening of acetylcholine-gated channels in end plate membrane ⬇️ Entry of mainly Na+ ions and to a lesser extent Ca2+ ions through these channels ⬇️ Development of end plate potential ⬇️ Local end plate potential when reaches a threshold magnitude, there is opening to voltage-gated sodium channels at the site ⬇️ Initiation of action potential in muscle fibre by end plate depolarization ⬇️ Propagation of action potential in muscle fibre along the surface and into the fibre along 'T' tubules ⬇️ Depolarization reaching at triads causing release of calcium into the sarcoplasm increasing calcium concentration above resting level ⬇️ Binding of calcium with troponin ⬇️ Initiation of muscle contraction
Neuromuscular Blockers
Neuromuscular transmission can be interrupted at various pre or post synaptic levels by drugs, chemicals, toxins etc. These are known as NMJ Blockers. Some examples:-
Presynaptic Blockers:- Botulinum Toxin, Hemicholinium
Postsynaptic Competitive Blockers- Curare, Gallamine
Postsynaptic Reversible Depolarising Blockers- Neostigmine, Physostigmine
Postsynaptic Irreversible Depolarising Blockers- Nerve gas, Sarin, Malathion, etc.