Synaptic contributions to cochlear outer hair cell Ca²⁺ homeostasis

Abstract

For normal cochlear function, outer hair cells (OHCs) require a precise regulation of intracellular Ca²⁺ levels. Influx of Ca²⁺ occurs both at the stereocillia tips and through the basolateral membrane. In this latter compartment, two different origins for Ca²⁺ influx have been poorly explored: voltage-gated Ca²⁺ 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, we report that these two Ca²⁺ entry sites are closely positioned, but present different regulation mechanisms. Ca²⁺ spread from MOC synapses is contained by cisternal Ca²⁺-ATPases. Considered a weak drive for transmitter release, we found that VGCC Ca²⁺ signals are larger than expected and can be potentiated by ryanodine receptors. Finally, we showed that sorcin, a highly expressed gene product in OHCs with reported Ca²⁺ control function in cardiomyocytes, regulates basal Ca²⁺ levels and MOC synaptic activity in OHCs.