The influence of presynaptic membrane potential on synaptic efficacy at the calyx of Held

Abstract

Various presynaptic modulations involve changes in the presynaptic membrane potential. However, it is not entirely clear how presynaptic membrane potential determines synaptic efficacy. We addressed this issue using simultaneous pre- and postsynaptic whole-cell recordings at the calyx of Held in rat brainstem slices. Gradual decrease in the presynaptic action potential amplitude by tetrodotoxin (TTX, 20-40 nM) had no effect on the EPSCs amplitude as far as the action potential overshoot exceeded +10 mV, but further reduction below this level steeply diminished EPSCs. In the absence of TTX, presynaptic depolarization (by 10-20 mV) increased the EPSC amplitude despite a reduction in the action potential amplitude, whereas presynaptic hyperpolarization had no clear effect on EPSCs. Presynaptic Ca²⁺ currents, recorded after blocking sodium and potassium conductance, underwent facilitation when the nerve terminal was depolarized (15-20 mV, 2 sec). Although this magnitude of depolarization did not evoke detectable Ca²⁺ currents, Ca²⁺ measurements using fluo-4 showed a clear increase in the Ca²⁺ concentration in the nerve terminal. These results suggest that presynaptic depolarization increases Ca²⁺ influx into the nerve terminal thereby facilitating transmitter release via mechanisms involving Ca²⁺ -dependent facilitation of Ca²⁺ currents. [Jpn J Physiol 55 Suppl:S152 (2005)]