Fast Ca 2+ signals at mouse inner hair cell synapse: a role for Ca 2+ ‐induced Ca 2+ release

Inner hair cells of the mammalian cochlea translate acoustic stimuli into ‘phase‐locked’ nerve impulses with frequencies of up to at least 1 kHz. Little is known about the intracellular Ca 2+ signal that links transduction to the release of neurotransmitter at the afferent synapse. Here, we use confocal microscopy to provide evidence that Ca 2+ ‐induced Ca 2+ release (CICR) may contribute to the mechanism. Line scan images (2 ms repetition rate) of neonatal mouse inner hair cells filled with the fluorescent indicator FLUO‐3, revealed a transient increase in intracellular Ca 2+ concentration ([Ca 2+ ] i ) during brief (5–50 ms) depolarizing commands under voltage clamp. The amplitude of the [Ca 2+ ] i transient depended upon the Ca 2+ concentration in the bathing medium in the range 0–1.3 m m . [Ca 2+ ] i transients were confined to a region near the plasma membrane at the base of the cell in the vicinity of the afferent synapses. The change in [Ca 2+ ] i appeared uniform throughout the entire basal sub‐membrane space and we were unable to observe hotspots of activity. Both the amplitude and the rate of rise of the [Ca 2+ ] i transient was reduced by external ryanodine (20 μ m ), an agent that blocks Ca 2+ release from the endoplasmic reticulum. Intracellular Cs + , commonly used to record at presynaptic sites, produced a similar effect. We conclude that both ryanodine and intracellular Cs + block CICR in inner hair cells. We discuss the contribution of CICR to the measured [Ca 2+ ] i transient, the implications for synaptic transmission at the afferent synapse and the significance of its sensitivity to intracellular Cs + .