Muscular Synaptic Transmission

Neuromuscular Junction (NMJ)

Motor information → spinal cord → ventral horn → somatic spinal nerve → myocyte (muscle)

A synapse between a motor neuron and a muscle. Communicates via acetylcholine (ACh). The post-synaptic neuron (on muscle cell) has junctional folds which increase the surface area of the synaptic cleft and increase the number of receptors. These also decrease the distance between cells, cutting down on travel time.

Electrical events

When activated, sodium enters the through the acetylcholine receptor (potassium won't move much because it sits around resting potential). This will depolarize the membrane (end plate) at the NMJ enough the trigger an action potential. The potential change is graded (not all-or-nothing) as more receptor activation results in more depolarization local to where the receptors are.

A quanta is the smallest unit of neurotransmitter which can be released at a time. The more quanta, the more depolarization.

• Quantal size: Response to one vesicle
• Quantal content: Number of vesicles released from the post-synaptic nerve
• M: Mean amplitude of responses

Reverse potential

As sodium enters the cell with an action potential, potassium will leave to stabilize the electrical gradient. This creates an electrical potential of 0 mV all told.

Miniature spontaneous synaptic events (MINIs)

There is the possibility the post-synaptic cell can experience spontaneous depolarization which occurs when individual ACh vesicles are released from the presynaptic cell without a presynaptic action potential (oops).

As the number of vesicles (and quanta of ACh) released will always be enough to trigger an action potential (e.g. the safety factor), this spontaneous event will affect the post-synaptic cell.

Acetylcholine Receptor

Made of 5 subunits forming an ion channel. Activates upon binding of two acetylcholine molecules and will desensitize rapidly.

Clinical pearls

Curare: Competitive antagonist for ACh. Reversible
Alpha-bungarotoxin: Competitive antagonist for ACh. Irreversible
Myasthenia Gravis: Autoimmune disease which targets ACh receptors, blocking them. Treated with Acetylcholinesterase inhibitor to increase ACh concentration in synapse

Calcium homeostasis

Calcium is bound through calmodulin, calcineurin, calreticulin, and synaptotagmin. It is sequestered (stored) in the SER and the mitochondria. It is released from the cell using either a Ca2+ ATPase or a Na/Ca antiporter (3-to-1 exchange) on the cell membrane.

The SER will pump Ca2+ inside via Ca-ATPase. It has a ryanodine receptor (stimulated by caffeine) and IP3 receptor, both of which will promote the release of calcium into the cytoplasm. The IP3 receptor will bind IP3 from PLA2.

The mitochondria will store calcium using a Na/Ca antiporter, although this process is low affinity.

Calcium channels