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Journal of neurophysiology

The temporal characteristics of Ca2+ entry through L-type and T-type Ca2+ channels shape exocytosis efficiency in chick auditory hair cells during development.


PMID 22972963

Abstract

During development, synaptic exocytosis by cochlear hair cells is first initiated by patterned spontaneous Ca(2+) spikes and, at the onset of hearing, by sound-driven graded depolarizing potentials. The molecular reorganization occurring in the hair cell synaptic machinery during this developmental transition still remains elusive. We characterized the changes in biophysical properties of voltage-gated Ca(2+) currents and exocytosis in developing auditory hair cells of a precocial animal, the domestic chick. We found that immature chick hair cells (embryonic days 10-12) use two types of Ca(2+) currents to control exocytosis: low-voltage-activating, rapidly inactivating (mibefradil sensitive) T-type Ca(2+) currents and high-voltage-activating, noninactivating (nifedipine sensitive) L-type currents. Exocytosis evoked by T-type Ca(2+) current displayed a fast release component (RRP) but lacked the slow sustained release component (SRP), suggesting an inefficient recruitment of distant synaptic vesicles by this transient Ca(2+) current. With maturation, the participation of L-type Ca(2+) currents to exocytosis largely increased, inducing a highly Ca(2+) efficient recruitment of an RRP and an SRP component. Notably, L-type-driven exocytosis in immature hair cells displayed higher Ca(2+) efficiency when triggered by prerecorded native action potentials than by voltage steps, whereas similar efficiency for both protocols was found in mature hair cells. This difference likely reflects a tighter coupling between release sites and Ca(2+) channels in mature hair cells. Overall, our results suggest that the temporal characteristics of Ca(2+) entry through T-type and L-type Ca(2+) channels greatly influence synaptic release by hair cells during cochlear development.

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M5441
Mibefradil dihydrochloride hydrate, ≥98% (HPLC), powder
C29H38FN3O3 · 2HCl · xH2O