title: Primary and secondary regulation of quantal transmitter release: calcium and sodium.
abstract: Calcium is the prime regulator of quantal acetylcholine liberation at the neuromuscular junction; its entry through the presynaptic membrane and the level of free [Ca]in most probably determine the number of transmitter quanta liberated by the nerve impulse. The level of free [Ca[in, in turn, is controlled by a number of subcellular elements: mitochondria, endoplasmic reticulum, vesicles, macromolecules and the surface membrane. The action potential induced calcium entry is not the only factor responsible for coupling nerve terminal depolarization with increased transmitter release; increased transmitter release occurs also in the virtual absence of calcium ions in the extracellular medium, when a reversed electrochemical gradient for calcium probably exists during action potential activity. Several lines of evidence suggest that the entry of sodium ions is responsible for this augmented transmitter release: the tetanic potentiation observed under reversed calcium gradient is blocked by tetrodotoxin; tetanic and post-tetanic potentiation are augmented and prolonged by ouabain; the amplitude of the extracellular nerve action potential is reduced with high-frequency stimulation, in parallel with increased spontaneous quantal release. In addition, sodium-filled egg-lecithin liposomes augment quantal liberation. The augmentory effect of sodium on transmitter release is probably due to an intracellular calcium translocation, since no preferred timing after the action potential is observed. Thus, the level of [Na]in in the presynaptic nerve terminal can control indirectly the efficiency of synaptic transmission.
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D007700:Kinetics; D008081:Liposomes; D008928:Mitochondria / Q000378:metabolism; D009119:Muscle Contraction; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology*
chemical_list: D008081:Liposomes; D018377:Neurotransmitter Agents; D012964:Sodium; D000109:Acetylcholine; D002118:Calcium