Synaptic contributions to cochlear hair cell Ca2+ dynamics

MARCELO J. MOGLIE; DIEGO WENGIER; A. BELEN ELGOYHEN; JUAN D. GOUTMAN

the journal of neuroscience

Society for Neuroscience

Año: 2021 vol. 41 p. 6812 - 6821

For normal cochlear function, outer hair cells (OHCs) require a precise control of intracellular Ca2+ levels. In the absence of regulatory elements such as proteinaceous buffers or extrusion pumps, OHCs degenerate, leading to profound hearing impairment. Influx of Ca2+ occurs both at the stereocilia tips and 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 910 cholinergic nicotinic receptors at synapses with medio-olivochlear complex (MOC) neurons. Using functional imaging in mouse OHCs, we dissected Ca2+ influx individually through each of these sources, either by applying step depolarizations to activate VGCC, or stimulating MOC axons. Ca2+ ions originated in MOC synapses, but not by VGCC activation, was confined by Ca2+-ATPases most likely present in nearby synaptic cisterns. Although Ca2+ currents in OHCs are small, VGCC Ca2+ signals were comparable in size to those elicited by 910 receptors, and were potentiated by ryanodine receptors. In contrast, no evidence of potentiation by ryanodine receptors was found for MOC Ca2+ signals over a wide range of presynaptic stimulation strengths. Our study shows that in spite of the fact that these two Ca2+ entry sites are closely positioned, they differ in their regulation by intracellular cisterns and/or organelles, suggesting the existence of well-tuned mechanisms to separate the two different OHC synaptic functions.