Contrasting anesthetic sensitivities of T-type Ca 2+ channels of reticular thalamic neurons and recombinant Ca v3.3 channels

Abstract

1 Reticular thalamocortical neurons express a slowly inactivating T-type Ca 2+ current that is quite similar to that recorded from recombinant Ca v3.3b (α1Ib) channels. These neurons also express abundant Ca v3.3 mRNA, suggesting that it underlies the native current. 2 Here, we test this hypothesis by comparing the anesthetic sensitivities of recombinant Ca v3.3b channels stably expressed in HEK 293 cells to native T channels in reticular thalamic neurons (nRT) from brain slices of young rats. 3 Barbiturates completely blocked both Ca v3.3 and nRT currents, with pentobarbital being about twice more potent in blocking Ca v3.3 currents. Isoflurane had about the same potency in blocking Ca v3.3 and nRT currents, but enflurane, etomidate, propofol, and ethanol exhibited 2-4 fold higher potency in blocking nRT vs Ca v3.3 currents. 4 Nitrous oxide (N 2O; laughing gas) blocked completely nRT currents with IC 50 of 20%, but did not significantly affect Ca v3.3 currents at four-fold higher concentrations. In addition, we observed that in lower concentration, N 2O reversibly increased nRT but not Ca v3.3 currents. 5 In conclusion, contrasting anesthetic sensitivities of Ca v3.3 and nRT T-type Ca 2+ channels strongly suggest that different molecular structures of Ca 2+ channels give rise to slowly inactivating T-type Ca 2+ currents. Furthermore, effects of volatile anesthetics and ethanol on slowly inactivating T-type Ca 2+ channel variants may contribute to the clinical effects of these agents.