Synaptic transmission 1: at the NMJ

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Chemical synapse

A junction where a presynaptic neuron releases a neurotransmitter that acts on a postsynaptic cell.

Electrical synapse

A gap-junction-mediated connection allowing direct ionic current flow between cells with very fast transmission.

Presynaptic neuron

The neuron that releases neurotransmitter into the synaptic cleft.

Postsynaptic cell

The target cell that expresses receptors responding to neurotransmitter.

Neuromuscular junction (NMJ)

The chemical synapse between a motor neuron and a skeletal muscle fibre.

Acetylcholine (ACh)

The neurotransmitter released at all vertebrate NMJs, including all domestic animal species.

Choline acetyltransferase (ChAT)

The enzyme in motor neurons that synthesises ACh.

Synaptic vesicles

Membrane-bound packets that store neurotransmitter in the presynaptic terminal.

Voltage-gated Ca2+ channels (Cav)

Channels in the presynaptic terminal that open during depolarisation, allowing Ca2+ influx that triggers vesicle fusion.

Exocytosis at NMJ

Ca2+-dependent fusion of ACh-containing vesicles with the presynaptic membrane to release neurotransmitter.

Endocytosis of vesicles

The recycling process that retrieves vesicle membrane after release and reforms synaptic vesicles.

Synaptic cleft

The ~50 nm gap between nerve terminal and muscle end-plate.

Motor endplate

Specialised postsynaptic membrane on skeletal muscle containing junctional folds and ACh receptors.

Junctional folds

Deep infoldings in the muscle membrane that increase surface area and localise ACh receptors densely.

Nicotinic ACh receptor (nAChR)

A ligand-gated ion channel in skeletal muscle activated by ACh and permeable to Na+ and K+.

End-plate potential (EPP)

The depolarisation produced by ACh acting on nAChRs at the NMJ.

Miniature end-plate potentials (MEPPs)

Small spontaneous depolarisations caused by release of single vesicles (“quanta”) of ACh.

Quantal release

Concept that transmitter is released in discrete packets (vesicles), each generating one MEPP.

Quantal content

The number of vesicles released during an EPP; typically ~100 at vertebrate NMJs.

Mean quantal response formula

m = n × p, where n = number of vesicles available, p = probability of release.

Low calcium effect on release

Low extracellular Ca2+ reduces probability of vesicle fusion, decreasing EPP amplitude and MEPP frequency.

nAChR ion permeability

The channel allows Na+ influx (dominant at rest) and K+ efflux; the net effect at resting endplate potential is depolarisation.

Muscle resting potential

Approximately –100 mV in skeletal muscle, much more negative than typical neurons.

Muscle threshold

Around –65 mV; EPPs normally exceed this threshold and trigger a muscle action potential.

Voltage-gated Na+ channels in muscle

Located at the base of junctional folds; activated by EPP to generate a muscle action potential.

Acetylcholinesterase (AChE)

Enzyme that rapidly breaks down ACh in the synaptic cleft to terminate the signal.

Curare

A competitive antagonist of nAChRs that reduces EPP amplitude and can cause paralysis.

Electrical synapses in animals

Crayfish giant synapse is a classic example; transmission is extremely fast and synchronous.

Gap junctions

Structures composed of connexins that directly connect cytoplasm of two cells for electrical coupling.

Connexons

Hexameric connexin assemblies forming half of a gap junction channel.

Synchronised firing

Electrical synapses enable groups of neurons or muscle cells to fire action potentials together.

NMJ reliability

A single motor neuron action potential reliably causes a muscle action potential—high safety factor.

Veterinary example: Myasthenia gravis

An autoimmune disease in dogs, cats, and humans where antibodies target nAChRs, reducing MEPP and EPP amplitude and causing muscle weakness.

Congenital myasthenia (animals)

Genetic defects in NMJ proteins found in dogs and some livestock species causing exercise-induced weakness.

Importance of NMJ in tendon reflexes

Functional NMJs are required for the quadriceps to contract during the knee-jerk reflex in all domestic mammals.

Clinical targeting of synapses

Drugs such as AChE inhibitors are used in both human and veterinary medicine to enhance NMJ transmission.