Human cardiac sodium channels are affected by pentobarbital.
OBJECTIVE
To investigate the response to general anaesthetics of different sodium channel subtypes, we examined the effects of pentobarbital, a close thiopental analogue, on single sodium channels from human ventricular muscle and compared them with existing data from human brain channels.


METHODS
Sodium channels from preparations of human ventricular muscle were incorporated into planar lipid bilayers in the presence of batrachotoxin, a sodium channel activator. Single channel currents were recorded in symmetrical 100 mmol L-1 and 500 mmol L-1 NaCl before and after the addition of the anaesthetic pentobarbital (0.34-1.34 mmol L-1).


RESULTS
The blocking effect of pentobarbital on the fractional open time had an IC50 of 690 micromol L-1 in 500 mmol L-1 NaCl, whereas it had a significantly lower IC50 of 400 micromol L-1 in 100 mmol L-1 NaCl. Pentobarbital caused a significant shift of steady-state activation to hyperpolarized potentials (fmax = -42 mV, IC50 = 2 mmol L-1). This effect was independent of NaCl concentration.


CONCLUSIONS
Despite pharmacological and electrophysiological differences between human cardiac and human brain sodium channels their responses to pentobarbital are similar. The finding of channel block being dependent on the electrolyte concentration is novel for sodium channels.
Wartenberg
H C
HC
Klinik und Poliklinik für Anästhesiologie und spezielle Intensivmedizin, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
Wartenberg
J P
JP
Urban
B W
BW
D000465:Algorithms; D001496:Batrachotoxins / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D018757:GABA Modulators / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008051:Lipid Bilayers; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010424:Pentobarbital / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D062687:Sodium Channel Agonists; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000187:drug effects*
D001496:Batrachotoxins; D018757:GABA Modulators; D008051:Lipid Bilayers; D011994:Recombinant Proteins; D062687:Sodium Channel Agonists; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D010424:Pentobarbital