Synaptic contributions to cochlear outer hair cell Ca ²⁺ homeostasis

For normal cochlear function, outer hair cells (OHCs) require a precise regulation of intracellular Ca ²⁺ levels. Influx of Ca ²⁺ occurs both at the stereocillia tips and through the basolateral membrane. In this latter compartment, two different origins for Ca ²⁺ influx have been poorly explored: voltage-gated Ca ²⁺ channels (VGCC) at synapses with type II afferent neurons, and α9α10 cholinergic nicotinic receptors at synapses with medio-olivochlear complex (MOC) neurons. Using functional imaging in rodent OHCs, we report that these two Ca ²⁺ entry sites are closely positioned, but present different regulation mechanisms. Ca ²⁺ spread from MOC synapses is contained by cisternal Ca ²⁺ -ATPases. Considered a weak drive for transmitter release, we unexpectedly found that VGCC Ca ²⁺ signals are comparable in size to those elicited by α9α10 and can be potentiated by ryanodine receptors. Finally, we showed that sorcin, a highly expressed gene product in OHCs with reported Ca ²⁺ control function in cardiomy-ocytes, regulates basal Ca ²⁺ levels and MOC synaptic activity in OHCs.