Calcium dependence of exocytosis and endocytosis at the Cochlear inner hair cell afferent synapse

Release of neurotransmitter at the inner hair cell (IHC) afferent synapse is a fundamental step in translating sound into auditory nerve excitation. To study the Ca2+ dependence of the underlying vesicle fusion and subsequent endocytosis, we combined Ca2+ uncaging with membrane capacitance measurements in mouse IHCs. Rapid elevations in [Ca2+](i) above 8 muM caused a biphasic capacitance increase corresponding to the fusion of similar to 40,000 vesicles. The kinetics of exocytosis displayed a fifth-order Ca2+ dependence reaching maximal rates of >3 x 10(7) vesicle/s. Exocytosis was always followed by slow, compensatory endocytosis (tau approximate to 15 s). Higher [Ca2+](i) increased the contribution of a faster mode of endocytosis with a Ca2+-independent time constant of similar to 300 ms. These properties provide for rapid and sustained transmitter release from this large presynaptic terminal.