CaV3.2 is the major molecular substrate for redox regulation of T-type Ca2+ channels in the rat and mouse thalamus

Pavle M Joksovic; Michael T Nelson; Vesna Jevtovic-Todorovic; Manoj K Patel; Edward Perez-Reyes; Kevin P Campbell; Chien-Chang Chen; Slobodan M Todorovic

doi:10.1113/jphysiol.2006.110395

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CaV3.2 is the major molecular substrate for redox regulation of T-type Ca2+ channels in the rat and mouse thalamus

Journal article

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CaV3.2 is the major molecular substrate for redox regulation of T-type Ca2+ channels in the rat and mouse thalamus

Pavle M Joksovic, Michael T Nelson, Vesna Jevtovic-Todorovic, Manoj K Patel, Edward Perez-Reyes, Kevin P Campbell, Chien-Chang Chen and Slobodan M Todorovic

The Journal of physiology, Vol.574(2), pp.415-430

07/15/2006

DOI: 10.1113/jphysiol.2006.110395

PMCID: PMC1817755

PMID: 16644797

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Abstract

Although T-type Ca(2+) channels in the thalamus play a crucial role in determining neuronal excitability and are involved in sensory processing and pathophysiology of epilepsy, little is known about the molecular mechanisms involved in their regulation. Here, we report that reducing agents, including endogenous sulfur-containing amino acid l-cysteine, selectively enhance native T-type currents in reticular thalamic (nRT) neurons and recombinant Ca(V)3.2 (alpha1H) currents, but not native and recombinant Ca(V)3.1 (alpha1G)- and Ca(V)3.3 (alpha1I)-based currents. Consistent with this data, T-type currents of nRT neurons from transgenic mice lacking Ca(V)3.2 channel expression were not modulated by reducing agents. In contrast, oxidizing agents inhibited all native and recombinant T-type currents non-selectively. Thus, our findings directly demonstrate that Ca(V)3.2 channels are the main molecular substrate for redox regulation of neuronal T-type channels. In addition, because thalamic T-type channels generate low-threshold Ca(2+) spikes that directly correlate with burst firing in these neurons, differential redox regulation of these channels may have an important function in controlling cellular excitability in physiological and pathological conditions and fine-tuning of the flow of sensory information into the central nervous system.

Membrane Potentials - drug effects

Calcium Channels, T-Type - physiology

Oxidation-Reduction

Calcium - metabolism

Gene Expression Regulation - physiology

Rats

Male

Mice, Transgenic

Membrane Potentials - physiology

Rats, Sprague-Dawley

Animals

Protein Isoforms - metabolism

Calcium Channels, T-Type - metabolism

Thalamus - physiology

Cysteine - pharmacology

Female

Calcium Channels, T-Type - genetics

Mice

Protein Isoforms - genetics

Details

Title: Subtitle: CaV3.2 is the major molecular substrate for redox regulation of T-type Ca2+ channels in the rat and mouse thalamus
Creators: Pavle M Joksovic - Department of Anesthesiology, University of Virginia Health System, Mail Box 800710, Charlottesville, VA 22908-0710, USA
Michael T Nelson
Vesna Jevtovic-Todorovic
Manoj K Patel
Edward Perez-Reyes
Kevin P Campbell
Chien-Chang Chen
Slobodan M Todorovic
Resource Type: Journal article
Publication Details: The Journal of physiology, Vol.574(2), pp.415-430
DOI: 10.1113/jphysiol.2006.110395
PMID: 16644797
PMCID: PMC1817755
NLM abbreviation: J Physiol
ISSN: 0022-3751
eISSN: 1469-7793
Publisher: England
Grant note: K08 DA000428 / NIDA NIH HHS Z01 DA000406 / Intramural NIH HHS R01 NS038691 / NINDS NIH HHS AG11355 / NIA NIH HHS P01 AG011355 / NIA NIH HHS K08-DA00428 / NIDA NIH HHS HD 44517 / NICHD NIH HHS GM070726 / NIGMS NIH HHS R01 GM070726 / NIGMS NIH HHS KO8-DA00406 / NIDA NIH HHS NS038691 / NINDS NIH HHS R01 HD044517 / NICHD NIH HHS
Language: English
Date published: 07/15/2006
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984020777402771

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