Isoflurane and sevoflurane modulate inactivation kinetics of Ca2+ currents in single bullfrog atrial myocytes.
BACKGROUND
To clarify the mechanism(s) of anesthetic depression of myocardial Ca2+ currents, the effects of isoflurane and sevoflurane on the inactivation kinetics of Ca2+ current in single bullfrog atrial myocytes were studied.


METHODS
Freshly isolated bullfrog atrial myocytes were obtained with an enzymatic dispersion procedure. Ca2+ currents were recorded with a whole-cell voltage-clamp technique.


RESULTS
Both isoflurane (1.25, 2.5, 5.0 vol%) and sevoflurane (2.5, 5.0 vol%) decreased the peak amplitude of Ca2+ current ICa with a minimal change in the time to peak and the reversal potential. The inactivation kinetics studies revealed that (1) isoflurane (2.5 vol%) and sevoflurane (5.0 vol%) markedly reduced the time constant of inactivation in ICa to 55% and 75% of control, respectively; (2) isoflurane (2.5 vol%) shifted the midpoint (V1/2) of steady-state inactivation curve of ICa toward negative by 2.3 mV; and (3) isoflurane (2.5 vol%) delayed the reactivation time constant of ICa to 119% of control. The further computer-simulation study demonstrated that the observed decrease of time constant by isoflurane (1.25, 2.5 vol%) and sevoflurane (2.5 vol%) can explain the reduction in amplitude of ICa.


CONCLUSIONS
The depression of ICa by lower concentration of isoflurane (1.25, 2.5 vol%) and sevoflurane (2.5 vol%) mainly is due to the decrease of time constant and, at higher concentration, isoflurane and sevoflurane may affect the other membrane components.
Hirota
K
K
Department of Anesthesiology, Toyama Medical and Pharmaceutical University School of Medicine, Japan.
Fujimura
J
J
Wakasugi
M
M
Ito
Y
Y
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004594:Electrophysiology; D004987:Ethers / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D007530:Isoflurane / Q000494:pharmacology*; D007700:Kinetics; D008738:Methyl Ethers; D009206:Myocardium / Q000378:metabolism*; D011892:Rana catesbeiana; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D015220:Calcium Channels; D004987:Ethers; D008738:Methyl Ethers; D000077149:Sevoflurane; D007530:Isoflurane