Synaptic Transmission & the NMJ

P/Q-type voltage-gated Ca²⁺ channels in the presynaptic terminal; Ca²⁺ entry is the transducer — no Ca²⁺, no transmission.

Release varies with roughly the 3rd–4th power of Ca²⁺ influx, so small changes in Ca²⁺ (or competing Mg²⁺) have dramatic effects.

Synaptotagmin binds Ca²⁺ and triggers the SNARE complex (synaptobrevin/VAMP, syntaxin, SNAP-25) to zipper membranes together.

N_M type: a pentamer (α₂βδε in adult muscle) that is itself a ligand-gated, non-selective cation channel; two ACh molecules (one per α subunit) must bind to open it.

The mixed Na⁺-in/K⁺-out cation current has a reversal potential near 0 mV, so the EPP depolarizes toward zero.

The EPP (40–70 mV) far exceeds the ~15 mV needed to reach threshold, guaranteeing 1:1 transmission — every nerve impulse produces a muscle twitch.

EPP is local, graded, non-propagating and chemically generated; the muscle AP is all-or-none, propagating, and generated by voltage-gated Na⁺ channels in the junctional folds.

Miniature end-plate potentials (~0.5–1 mV) from spontaneous single-vesicle fusion; they support Katz's quantal hypothesis — an EPP is ~100–200 quanta at once.

Fewer MEPPs of normal amplitude = presynaptic release problem; normal frequency but small amplitude = postsynaptic receptor problem.

Acetylcholinesterase in the basal lamina hydrolyzes ACh within ~1 ms; choline reuptake by the presynaptic Na⁺-dependent choline transporter is the rate-limiting step of synthesis.

Almost entirely Ca²⁺ channel opening and vesicle fusion, not diffusion across the ~50 nm cleft.