Temperature-independent Inhibition of L-type calcium currents by halothane and sevoflurane in human atrial cardiomyocytes.
BACKGROUND
Cardiac L-type calcium currents (ICa,L) are affected by volatile anesthetics, possibly contributing to their side effects. Actions of anesthetics on ion channels are usually studied in vitro at room temperature. However, the solubility of anesthetic gases as well as ICa,L are markedly sensitive to the study temperature. Therefore, temperature-dependent effects of halothane and sevoflurane on cardiac ICa,L were analyzed.


METHODS
ICa,L were studied at 21 degrees C and 36 degrees C with the patch clamp technique in isolated human atrial cardiomyocytes. Concentrations of anesthetics brought into solution by gassing at both temperatures were determined with gas chromatography.


RESULTS
The aqueous concentrations of halothane and sevoflurane were linearly related to their concentration in the gas phase (1 to 3 minimum alveolar concentration [MAC]). At 21 degrees C, the slope of this relation was 0.52 and 0.12 mm/vol % for halothane and sevoflurane, respectively, and decreased at 36 degrees C to 0.29 and 0.09 mm/vol %, respectively. ICa,L displayed significantly higher current amplitudes at 36 degrees C than at 21 degrees C and significantly accelerated time-dependent inactivation. Halothane (1-2 MAC) and sevoflurane (1-3 MAC) evoked stronger inhibitions of ICa,L at 21 degrees C than at 36 degrees C. In spite of different temperature-dependent current amplitudes, the fractional (percent) inhibition of ICa,L showed the same linear relationship to the concentrations of halothane and sevoflurane in the bath medium at both temperatures, as revealed from present and previous experiments.


CONCLUSIONS
Inhibition of ICa,L by halothane and sevoflurane is determined by the aqueous concentration of the anesthetics, independently of the temperature. Increased solubility may explain the stronger effects of the anesthetics at lower temperatures.
University Hospital, Rheinisch-Westfälische Technische Hochschule, Aachen, Germany.
Rocco
R
Hüneke
Daniela
D
Zitzelsberger
Jens
J
Fassl
Eberhard
E
Jüngling
Stefan
S
Brose
Wolfgang
W
Buhre
Rolf
R
Rossaint
Andreas
A
Lückhoff
D000465:Algorithms; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000502:physiology; D006221:Halothane / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D008564:Membrane Potentials; D008738:Methyl Ethers / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D000077149:Sevoflurane; D012996:Solutions; D013696:Temperature; D014978:Xenon / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D008738:Methyl Ethers; D012996:Solutions; D000077149:Sevoflurane; D014978:Xenon; D006221:Halothane