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Ca V 3.2 is the major molecular substrate for redox regulation of T‐type Ca 2+ channels in the rat and mouse thalamus
Author(s) -
Joksovic Pavle M.,
Nelson Michael T.,
JevtovicTodorovic Vesna,
Patel Manoj K.,
PerezReyes Edward,
Campbell Kevin P.,
Chen ChienChang,
Todorovic Slobodan M.
Publication year - 2006
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.110395
Subject(s) - chemistry , neuroscience , biophysics , thalamus , redox , biochemistry , biology , organic chemistry
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 (α1H) currents, but not native and recombinant Ca V 3.1 (α1G)‐ and Ca V 3.3 (α1I)‐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.