Evaluation of synaptic Ca2+ signals of opposite sign in cochlear outer hair cells

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

Congreso; XXXIV Reunión Anual de la SAN; 2019

Cochlear outer hair cells (OHCs) are responsible for controlling the gain of auditory inputs by means of a unique cellular property that allows them to alter their shape in response to voltage changes. This function is modulated by a cholinergic input coming from the brainstem and mediated by the Ca2+ permeable α9α10 nicotinic receptor. Ca2+ influx through this receptor is coupled to the activation of Ca2+-dependent K+ channels within a very narrow domain limited by a near-membrane postsynaptic cistern. Thus, cholinergic activity hyperpolarizes the OHC and inhibits cochlear amplification. We aimed to determine the magnitude and spread of synaptic Ca2+ signals and the role of the synaptic cisterns using simultaneous electrophysiological recordings and Ca2+ imaging techniques. Electrical stimulation of axons revealed single efferent Ca2+ entry sites. The amplitude of the signal correlated with that of the evoked postsynaptic currents and it was dependent on efferent stimulation frequency. Moreover, pharmacological manipulations suggested a possibly role for Ca2+ extrusion mechanisms in Ca2+ signal termination. Finally, OHC depolarizations activated voltage-gated Ca2+ channels producing local Ca2+ levels similar to those obtained by the cholinergic input. Since OHCs present afferent glutamatergic innervation and presynaptic active zones are closely positioned to efferent synaptic cisterns, Ccrosstalk between these two synapses will be discussed.