Effects of the anesthetic gases xenon, halothane, and isoflurane on calcium and potassium currents in human atrial cardiomyocytes.
BACKGROUND
Negative inotropic and proarrhythmic side effects on the heart are well known for the volatile anesthetics halothane and isoflurane but not for the noble gas xenon. We investigated the effects of halothane, isoflurane, and xenon on calcium and potassium currents in human atrial myocytes to elucidate the cellular and molecular basis of their cardiac actions.


METHODS
Atrial myocytes were prepared from the right auricles obtained from patients undergoing heart surgery. Ion currents were measured with the whole cell patch clamp technique during superfusion of the cells with solutions that contained halothane, isoflurane, or xenon at concentrations corresponding to their respective minimum alveolar concentration (MAC); gas concentrations were determined with the head space-gas chromatography/mass spectrometry/selected ion monitoring method.


RESULTS
L-type calcium currents were significantly depressed by 31.9 +/- 4.1%, from -1.8 +/- 0.3 to -1.2 +/- 0.4 picoampere (pA)/picofarad (pF) (n = 4; P < 0.05) at 1 MAC halothane and by 21.7 +/- 9.2%, from -1.6 +/- 0.7 to -1.2 +/- 0.6 pA/pF (n = 7; P < 0.05) at 1 MAC isoflurane, but not affected by 70% xenon (1 MAC). Inwardly rectifying potassium currents were not influenced by any anesthetic. Halothane (1 MAC) significantly inhibited the transient as well as the sustained part of voltage-gated potassium outward currents, by 19.4 +/- 6.7%, from 6.7 +/- 2.1 to 5.4 +/- 1.6 pA/pF (n = 8; P < 0.05), and by 8.6 +/- 4.8%, from 5.5 +/- 1.7 to 5.0 +/- 1.5 pA/pF (n = 8; P < 0.05), respectively. Transient K+ outward currents were even more inhibited, by 25.8 +/- 4.8%, from 9.8 +/- 3.1 to 7.3 +/- 2.1 pA/pF (n = 5; P < 0.05) at 1 MAC isoflurane, whereas xenon evoked only a slight (albeit significant) inhibition, by 6.1 +/- 3.7%, from 8.2 +/- 6.0 to 7.7 +/- 5.8 pA/pF (n = 10; P < 0.05). Isoflurane and xenon did not affect sustained potassium currents. All effects of the anesthetics were fully reversible after washout.


CONCLUSIONS
Halothane and isoflurane exhibited considerable inhibitory effects on voltage-gated cardiac Ca2+ and K+ currents important for the duration of action potentials and the repolarization. Xenon, in contrast, did not affect Ca2+ currents and only slightly inhibited transient K+ outward currents, in line with the almost absent cardiac side effects of the noble gas.
Hüneke
R
R
Department of Anesthesiology, University Hospital Rheinisch-Westfällische Technische Hochschule Aachen, Germany.
Jüngling
E
E
Skasa
M
M
Rossaint
R
R
Lückhoff
A
A
D000368:Aged; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D002315:Cardiopulmonary Bypass; D002469:Cell Separation; D005260:Female; D006221:Halothane / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008875:Middle Aged; D009206:Myocardium / Q000166:cytology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D014978:Xenon / Q000494:pharmacology*
D018685:Anesthetics, Inhalation; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D015221:Potassium Channels; D014978:Xenon; D007530:Isoflurane; D006221:Halothane