Blocking effects of the anaesthetic etomidate on human brain sodium channels.
Sodium channels from human brain tissue were incorporated into voltage-clamped planar lipid bilayers in presence of batrachotoxin and exposed to increasing concentrations of the intravenous anaesthetic drug etomidate (0.03-1.02 mM). Etomidate interacted with the sodium-conducting pathway of the channel causing a concentration-dependent block of the time-averaged sodium conductance (computer fit of the concentration-response curve: half-maximal blocking concentration, EC50, 0.19 mM; maximal block, block(max), 38%). This block of sodium-conductance resulted from two distinct effects (I) major effect: reduction of the sodium-channel amplitude and (II) minor effect: reduction of the fractional channel open-time. These results were observed at concentrations above clinically-relevant serum concentrations (up to 0.01 mM), suggesting only a limited role for human brain sodium channels in the mechanism of action of etomidate during clinical anaesthesia.
Frenkel
C
C
Klinik und Poliklinik für Anästhesiologie und Spezielle Intensivmedizin, Rheinische Friedrich-Wilhelms Universität Bonn, Germany.
Weckbecker
K
K
Wartenberg
H C
HC
Duch
D S
DS
Urban
B W
BW
D001496:Batrachotoxins / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005045:Etomidate / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D018408:Patch-Clamp Techniques; D012964:Sodium / Q000493:pharmacokinetics*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*
D001496:Batrachotoxins; D015222:Sodium Channels; D012964:Sodium; D005045:Etomidate