Contrasting anesthetic sensitivities of T-type Ca super(2+) channels of reticular thalamic neurons and recombinant Ca sub(v)3.3 channels

Reticular thalamocortical neurons express a slowly inactivating T-type Ca super(2+) current that is quite similar to that recorded from recombinant Ca sub(v)3.3b ( alpha 1Ib) channels. These neurons also express abundant Ca sub(v)3.3 mRNA, suggesting that it underlies the native current. Here, we test this hypothesis by comparing the anesthetic sensitivities of recombinant Ca sub(v)3.3b 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 Ca sub(v)3.3 and nRT currents, with pentobarbital being about twice more potent in blocking Ca sub(v)3.3 currents. Isoflurane had about the same potency in blocking Ca sub(v)3.3 and nRT currents, but enflurane, etomidate, propofol, and ethanol exhibited 2-4 fold higher potency in blocking nRT vs Ca sub(v)3.3 currents. Nitrous oxide (N sub(2)O; laughing gas) blocked completely nRT currents with IC sub(50) of 20%, but did not significantly affect Ca sub(v)3.3 currents at four-fold higher concentrations. In addition, we observed that in lower concentration, N sub(2)O reversibly increased nRT but not Ca sub(v)3.3 currents. In conclusion, contrasting anesthetic sensitivities of Ca sub(v)3.3 and nRT T-type Ca super(2+) channels strongly suggest that different molecular structures of Ca super(2+) channels give rise to slowly inactivating T-type Ca super(2+) currents. Furthermore, effects of volatile anesthetics and ethanol on slowly inactivating T-type Ca super(2+) channel variants may contribute to the clinical effects of these agents.