INVESTIGADORES
GOUTMAN Juan Diego
artículos
Título:
Synaptic contributions to cochlear hair cell Ca2+ dynamics
Autor/es:
MARCELO J. MOGLIE; DIEGO WENGIER; A. BELEN ELGOYHEN; JUAN D. GOUTMAN
Revista:
the journal of neuroscience
Editorial:
Society for Neuroscience
Referencias:
Año: 2021 vol. 41 p. 6812 - 6821
Resumen:
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 910 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 910 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.