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.
Rehberg
B
B
Department of Anesthesiology, Cornell University Medical Center, New York, NY 10021.
Duch
D S
DS
Urban
B W
BW
D001496:Batrachotoxins / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism; D008564:Membrane Potentials; D010424:Pentobarbital / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects*
D001496:Batrachotoxins; D008051:Lipid Bilayers; D015222:Sodium Channels; D010424:Pentobarbital