Mechanisms underlying short-term modulation of transmitter release by presynaptic depolarization.
Presynaptic terminal depolarization modulates the efficacy of transmitter release. Residual Ca2+ remaining after presynaptic depolarization is thought to play a critical role in facilitation of transmitter release, but its downstream mechanism remains unclear. By making simultaneous pre- and postsynaptic recordings at the rodent calyx of Held synapse, we have investigated mechanisms involved in the facilitation and depression of postsynaptic currents induced by presynaptic depolarization. In voltage-clamp experiments, cancellation of the Ca2+-dependent presynaptic Ca2+ current (I(pCa)) facilitation revealed that this mechanism can account for 50% of postsynaptic current facilitation, irrespective of intraterminal EGTA concentrations. Intraterminal EGTA, loaded at 10 mM, failed to block postsynaptic current facilitation, but additional BAPTA at 1 mM abolished it. Potassium-induced sustained depolarization of non-dialysed presynaptic terminals caused a facilitation of postsynaptic currents, superimposed on a depression, with the latter resulting from reductions in presynaptic action potential amplitude and number of releasable vesicles. We conclude that presynaptic depolarization bidirectionally modulates transmitter release, and that the residual Ca2+ mechanism for synaptic facilitation operates in the immediate vicinity of voltage-gated Ca2+ channels in the nerve terminal.
Hori
Tetsuya
T
Department of Neurophysiology, Doshisha University Faculty of Life and Medical Sciences, Kyoto 610-0394, Japan.
Takahashi
Tomoyuki
T
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009411:Nerve Endings / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D017661:Receptors, Presynaptic / Q000502:physiology*
D015220:Calcium Channels; D002614:Chelating Agents; D018377:Neurotransmitter Agents; D017661:Receptors, Presynaptic; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium