Dataset Information

Expression of voltage-gated calcium channel ?(2)?(4) subunits in the mouse and rat retina.

ABSTRACT: High-voltage activated Ca channels participate in multiple cellular functions, including transmitter release, excitation, and gene transcription. Ca channels are heteromeric proteins consisting of a pore-forming ?(1) subunit and auxiliary ?(2)? and ? subunits. Although there are reports of ?(2)?(4) subunit mRNA in the mouse retina and localization of the ?(2)?(4) subunit immunoreactivity to salamander photoreceptor terminals, there is a limited overall understanding of its expression and localization in the retina. ?(2)?(4) subunit expression and distribution in the mouse and rat retina were evaluated by using reverse transcriptase polymerase chain reaction, western blot, and immunohistochemistry with specific primers and a well-characterized antibody to the ?(2)?(4) subunit. ?(2)?(4) subunit mRNA and protein are present in mouse and rat retina, brain, and liver homogenates. Immunostaining for the ?(2)?(4) subunit is mainly localized to Müller cell processes and endfeet, photoreceptor terminals, and photoreceptor outer segments. This subunit is also expressed in a few displaced ganglion cells and bipolar cell dendrites. These findings suggest that the ?(2)?(4) subunit participates in the modulation of L-type Ca(2+) current regulating neurotransmitter release from photoreceptor terminals and Ca(2+)-dependent signaling pathways in bipolar and Müller cells.

SUBMITTER: De Sevilla Muller LP

PROVIDER: S-EPMC3748150 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Expression of voltage-gated calcium channel α(2)δ(4) subunits in the mouse and rat retina.

De Sevilla Müller Luis Pérez LP Liu Janelle J Solomon Alexander A Rodriguez Allen A Brecha Nicholas C NC

The Journal of comparative neurology 20130801 11

High-voltage activated Ca channels participate in multiple cellular functions, including transmitter release, excitation, and gene transcription. Ca channels are heteromeric proteins consisting of a pore-forming α(1) subunit and auxiliary α(2)δ and β subunits. Although there are reports of α(2)δ(4) subunit mRNA in the mouse retina and localization of the α(2)δ(4) subunit immunoreactivity to salamander photoreceptor terminals, there is a limited overall understanding of its expression and localiz ...[more]

PMID: 23296739

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Project description: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(V)1.3, Ca(V)2.2, and Ca(V)3.3). Further characterization of neuron-specific α-subunits showed that Ca(V)1.3 and Ca(V)3.3 were tonotopically-distributed, whereas Ca(V)2.2 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(V)2.3, Ca(V)3.1) from loose (Ca(V)1.2) 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.

Dataset Information

Expression of voltage-gated calcium channel ?(2)?(4) subunits in the mouse and rat retina.

Publications

Expression of voltage-gated calcium channel α(2)δ(4) subunits in the mouse and rat retina.

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