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 Ca 2+ dependence of the underlying vesicle fusion and subsequent endocytosis, we combined Ca 2+ uncaging with membrane capacitance measurements in mouse IHCs. Rapid elevations in [Ca 2+] i above 8 μM caused a biphasic capacitance increase corresponding to the fusion of ∼40,000 vesicles. The kinetics of exocytosis displayed a fifth-order Ca 2+ dependence reaching maximal rates of >3 × 10 7 vesicle/s. Exocytosis was always followed by slow, compensatory endocytosis (τ ≅ 15 s). Higher [Ca 2+] i increased the contribution of a faster mode of endocytosis with a Ca 2+-independent time constant of ∼300 ms. These properties provide for rapid and sustained transmitter release from this large presynaptic terminal.