Complex distribution patterns of voltage-gated calcium channel α-subunits in the spiral ganglion

Wei Chun Chen, Hui Zhong Xue, Yun Lucy Hsu, Qing Liu, Shail Patel, Robin L. Davis

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

As with other elements of the peripheral auditory system, spiral ganglion neurons display specializations that vary as a function of location along the tonotopic axis. Previous work has shown that voltage-gated K + channels and synaptic proteins show graded changes in their density that confers rapid responsiveness to neurons in the high frequency, basal region of the cochlea and slower, more maintained responsiveness to neurons in the low frequency, apical region of the cochlea. In order to understand how voltage-gated calcium channels (VGCCs) may contribute to these diverse phenotypes, we identified the VGCC α-subunits expressed in the ganglion, investigated aspects of Ca 2+-dependent neuronal firing patterns, and mapped the intracellular and intercellular distributions of seven VGCC α-subunits in the spiral ganglion in vitro.Initial experiments with qRT-PCR showed that eight of the ten known VGCC α-subunits were expressed in the ganglion and electrophysiological analysis revealed firing patterns that were consistent with the presence of both LVA and HVA Ca 2+ channels. Moreover, we were able to study seven of the α-subunits with immunocytochemistry, and we found that all were present in spiral ganglion neurons, three of which were neuron-specific (Ca V1.3, Ca V2.2, and Ca V3.3). Further characterization of neuron-specific α-subunits showed that Ca V1.3 and Ca V3.3 were tonotopically-distributed, whereas Ca V2.2 was uniformly distributed in apical and basal neurons. Multiple VGCC α-subunits were also immunolocalized to Schwann cells, having distinct intracellular localizations, and, significantly, appearing to distinguish putative compact (Ca V2.3, Ca V3.1) from loose (Ca V1.2) myelin.Electrophysiological evaluation of spiral ganglion neurons in the presence of TEA revealed Ca 2+ plateau potentials with slopes that varied proportionately with the cochlear region from which neurons were isolated. Because afterhyperpolarizations were minimal or absent under these conditions, we hypothesize that differential density and/or kinetics of one or more of the VGCC α-subunits could account for observed tonotopic differences. These experiments have set the stage for defining the clear multiplicity of functional control in neurons and Schwann cells of the spiral ganglion.

Original languageEnglish (US)
Pages (from-to)52-68
Number of pages17
JournalHearing Research
Volume278
Issue number1-2
DOIs
StatePublished - Aug 2011

All Science Journal Classification (ASJC) codes

  • Sensory Systems

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