title: CaV3.2 is the major molecular substrate for redox regulation of T-type Ca2+ channels in the rat and mouse thalamus.
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.
authors.affiliation: Department of Anesthesiology, University of Virginia Health System, Mail Box 800710, Charlottesville, VA 22908-0710, USA.
authors.forename: Pavle M
authors.initials: PM
authors.lastname: Joksovic
authors.forename: Michael T
authors.initials: MT
authors.lastname: Nelson
authors.forename: Vesna
authors.initials: V
authors.lastname: Jevtovic-Todorovic
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Patel
authors.forename: Edward
authors.initials: E
authors.lastname: Perez-Reyes
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Campbell
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Chen
authors.forename: Slobodan M
authors.initials: SM
authors.lastname: Todorovic
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D003545:Cysteine / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D010084:Oxidation-Reduction; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000502:physiology*
chemical_list: C504883:Cacna1h protein, mouse; C509958:Cacna1h protein, rat; D020747:Calcium Channels, T-Type; D020033:Protein Isoforms; D003545:Cysteine; D002118:Calcium