Effects of inhalational anesthetics on L-type Ca2+ currents in human atrial cardiomyocytes during beta-adrenergic stimulation.
BACKGROUND
Anesthetics may cause cardiac side effects by their action on L-type Ca2+ channels. Direct effects on the channels have not yet been discriminated from an interference with the beta-adrenergic channel regulation. The authors therefore studied the effects of halothane, sevoflurane, and xenon on human cardiac Ca2+ currents during stimulation with isoproterenol.


METHODS
Currents through L-type Ca2+ channels were measured with the patch clamp technique in atrial cardiomyocytes obtained from patients undergoing cardiac surgery. Cells were superfused with solutions equilibrated with anesthetics at the desired concentrations. Ca2+ currents during pulses to 10 mV were evaluated with respect to their peak value (I(max)) and to the total moved charge (Q).


RESULTS
In the absence and in the presence of isoproterenol (1 microm), sevoflurane (0.29 mm, 1 minimum alveolar concentration [MAC]) significantly depressed Q by 37.8 +/- 7.2% (mean +/- SD) and 40.8 +/- 10.3%, respectively. I(max) was not significantly affected in comparison with control cells never exposed to an anesthetic. Xenon (65%, 1 MAC) did not evoke significant effects. Exposure to halothane (0.39 mm, 1 MAC) during stimulation with isoproterenol significantly reduced Q by 31.3 +/- 23.3% (but not I(max)). After washout of halothane, Q was increased above the level prior to the application of halothane. Moreover, whereas Q promptly declined to baseline levels after washout of isoproterenol in controls, the previous exposure to halothane markedly delayed this decline, leaving Q significantly elevated for several minutes.


CONCLUSIONS
Halothane exerts a dual effect on Ca2+ currents. The long-lasting stimulatory effect may contribute to the proarrhythmic potency of the drug that exceeds that of sevoflurane, which only depressed Ca2+ currents.
Fassl
Jens
J
Department of Anesthesiology, Institute of Physiology, University Hospital, Aachen, Germany.
Halaszovich
Christian R
CR
Hüneke
Rocco
R
Jüngling
Eberhard
E
Rossaint
Rolf
R
Lückhoff
Andreas
A
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000465:Algorithms; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D002469:Cell Separation; D005260:Female; D006221:Halothane / Q000494:pharmacology; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008738:Methyl Ethers / Q000494:pharmacology; D008875:Middle Aged; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D000077149:Sevoflurane; D014978:Xenon / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D018685:Anesthetics, Inhalation; D020746:Calcium Channels, L-Type; D008738:Methyl Ethers; D000077149:Sevoflurane; D014978:Xenon; D007545:Isoproterenol; D006221:Halothane