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Semaphorin 3A induces acute changes in membrane excitability in spiral ganglion neurons in vitro
Author(s) -
Wong Victor S. C.,
Meadows Marc,
Goldberg David,
Willis Dianna E.
Publication year - 2019
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.14360
Subject(s) - sema3a , semaphorin , neuroscience , membrane potential , spiral ganglion , chemistry , patch clamp , biophysics , cochlea , biology , microbiology and biotechnology , electrophysiology , biochemistry , receptor
The development and survival of spiral ganglion neurons ( SGN s) are dependent on multiple trophic factors as well as membrane electrical activity. Semaphorins (Sema) constitute a family of membrane‐associated and secreted proteins that have garnered significant attention as a potential SGN “navigator” during cochlea development. Previous studies using mutant mice demonstrated that Sema3A plays a role in the SGN pathfinding. The mechanisms, however, by which Sema3A shapes SGN s firing behavior are not known. In these studies, we found that Sema3A plays a novel role in regulating SGN resting membrane potential and excitability. Using dissociated SGN from pre‐hearing (P3–P5) and post‐hearing mice (P12–P15), we recorded membrane potentials using whole‐cell patch clamp recording techniques in apical and basal SGN populations. Recombinant Sema3A was applied to examine the effects on intrinsic membrane properties and action potentials evoked by current injections. Apical and basal SGN s from newborn mice treated with recombinant Sema3A (100 ng/ml) displayed a higher resting membrane potential, higher threshold, decreased amplitude, and prolonged latency and duration of spikes. Although a similar phenomenon was observed in SGN s from post‐hearing mice, the resting membrane potential was essentially indistinguishable before and after Sema3A exposure. Sema3A‐mediated changes in membrane excitability were associated with a significant decrease in K + and Ca 2+ currents. Sema3A acts through linopirdine‐sensitive K + channels in apical, but not in the basal SGN s. Therefore, Sema3A induces differential effects in SGN membrane excitability that are dependent on age and location, and constitutes an additional early and novel effect of Sema3A SGN s in vitro.