Notes on Synaptic Transmission and NMJ

Motor neuron diseases can cause weak muscle contraction.
Acetylcholine (ACh) at the NMJ is rapidly inactivated in the synaptic cleft by acetylcholinesterase (AChE) breaking it down into choline and acetate; choline is then taken back up into the presynaptic terminal for reuse.
Other neurotransmitters are not degraded in the synapse in the same way; they are typically cleared by reuptake through specific transporters into the presynaptic neuron or surrounding glia.
If neurotransmitter is not bound to a receptor or not broken down, it can diffuse away into the bloodstream and be deactivated in the liver.
Key concept: presynaptic release and postsynaptic response are tightly regulated by release, receptor binding, and clearance mechanisms.

Action potentials are all-or-none and have the same amplitude; they trigger a stereotyped number of voltage-gated calcium channels to open in the presynaptic terminal.
With the same Ca^{2+} entry, the same number of vesicles (quanta) are released per action potential (AP).
Each vesicle contains a uniform amount of transmitter; thus, each AP produces a consistent quantal release into the synapse and a consistent postsynaptic response profile, assuming receptor responsiveness is constant.
Conceptual formula (quantal content): $m = n \, p$ where
- $m$ = mean number of vesicles released (quanta) per AP,
- $n$ = number of readily releasable vesicles,
- $p$ = release probability per vesicle.
In the NMJ, this quantal release translates into an end-plate potential (EPP) that feeds into postsynaptic nicotinic receptors.

Nicotinic ACh receptors at the NMJ are permeable to Na^+ and K^+.
Depolarization occurs because there is a large driving force for Na^+ influx (relative to K^+ efflux).
Driving forces (illustrative values):
- Driving force for Na^+:
  $$DF{Na} = Vm - E_{Na} \