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Received March 27, 2006
Revised April 7, 2006
Accepted after revision April 20, 2006
1 UVA Anesthesiology
2 University of Virginia
3 UVA Pharmacology
4 University of Iowa
5 IBS, Nankang, Taiwan
* To whom correspondence should be addressed. E-mail: st9d{at}virginia.edu.
Although T-type Ca2+ 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 CaV3.2 currents, but not native and recombinant CaV3.1- and CaV3.3-based currents. Consistent with this data, T-type currents of nRT neurons from transgenic mice lacking CaV3.2 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 CaV3.2 channels are the main molecular substrate for redox regulation of neuronal T-type channels. In addition, because thalamic T-type channels generate low-threshold Ca2+ 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.
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