Barbiturates depress currents through human brain calcium channels studied in Xenopus oocytes.

Barbiturates have had wide use as sedatives, anesthetics and anticonvulsants. Among the sites implicated in the membrane action of barbiturates are the gamma-aminobutyric acidA receptor, receptors for excitatory amino acids and Ca and potassium channels. The expression in Xenopus oocytes of various ligand- and voltage-gated channels offers the opportunity for more-detailed studies of such neuroactive substances as the barbiturates. Using RNA from human temporal cortex, we obtained the expression of an omega-conotoxin-sensitive, dihydropyridine-resistant Ca channel in Xenopus oocytes. Under voltage clamp, barbiturates depressed both the peak current and the steady-state current through this Ca channel. Barbiturates had no effect on the shape of the current-voltage relation, nor did they cause a shift in the voltage-dependence of channel activation. However, both the rate of inactivation of open Ca channels, as well as the proportion of channels inactivated at steady state were increased by barbiturates. The IC50 for these effects was about 0.25 mM for the more potent barbiturates tested. These results are consistent with the hypothesis that sedative and anesthetic effects of barbiturates can be mediated in part by an action to depress Ca currents.