The voltage-dependent action of pentobarbital on batrachotoxin-modified human brain sodium channels

The voltage-dependent action of the intravenous anesthetic pentobarbital on human brain sodium channels activated by batrachotoxin was examined using planar lipid bilayer methods. Fractional open time-data were fitted by Boltzmann functions to yield simple parameters characterizing the voltage-dependence of the fractional open time. Pentobarbital caused a dose-dependent reduction of the maximum fractional open time of the sodium channel and a shift of the potential of half-maximal open time towards hyperpolarized potentials, whereas the slope parameter of the Boltzmann-fits was unaffected. A statistically significant increase of the variability of these parameters was found only in the case of the maximum fractional open time, indicating a random fluctuation of pentobarbital-induced suppression of the sodium channels over time. The voltage-dependent action of pentobarbital probably results from either a pentobarbital-modification of channel activation gating and/or a modification of the pentobarbital action by the gating process itself.