Contrasting anesthetic sensitivities of T‐type Ca2+ channels of reticular thalamic neurons and recombinant Cav3.3 channels

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Abstract
Reticular thalamocortical neurons express a slowly inactivating T‐type Ca2+ current that is quite similar to that recorded from recombinant Cav3.3b (α1Ib) channels. These neurons also express abundant Cav3.3 mRNA, suggesting that it underlies the native current. Here, we test this hypothesis by comparing the anesthetic sensitivities of recombinant Cav3.3b channels stably expressed in HEK 293 cells to native T channels in reticular thalamic neurons (nRT) from brain slices of young rats. Barbiturates completely blocked both Cav3.3 and nRT currents, with pentobarbital being about twice more potent in blocking Cav3.3 currents. Isoflurane had about the same potency in blocking Cav3.3 and nRT currents, but enflurane, etomidate, propofol, and ethanol exhibited 2–4 fold higher potency in blocking nRT vs Cav3.3 currents. Nitrous oxide (N2O; laughing gas) blocked completely nRT currents with IC50 of 20%, but did not significantly affect Cav3.3 currents at four‐fold higher concentrations. In addition, we observed that in lower concentration, N2O reversibly increased nRT but not Cav3.3 currents. In conclusion, contrasting anesthetic sensitivities of Cav3.3 and nRT T‐type Ca2+ channels strongly suggest that different molecular structures of Ca2+ channels give rise to slowly inactivating T‐type Ca2+ currents. Furthermore, effects of volatile anesthetics and ethanol on slowly inactivating T‐type Ca2+ channel variants may contribute to the clinical effects of these agents. British Journal of Pharmacology (2005) 144, 59–70. doi:10.1038/sj.bjp.0706020