Halothane and sevoflurane inhibit Na/Ca exchange current in rat ventricular myocytes.
BACKGROUND
The electrogenic Na+/Ca2+ exchanger (NCX) represents the main extrusion pathway for Ca2+ in ventricular muscle and therefore plays an important role in the regulation of cytosolic Ca2+ and contraction. Halothane and sevoflurane modulate cytosolic Ca2+ regulation and at steady state are negatively inotropic, however, the involvement of anaesthetic-induced changes in NCX activity in these effects requires further study.


METHODS
Ventricular myocytes were isolated using a standard collagenase/protease dispersion technique and superfused with a physiological salt solution at 30 degrees C. Whole-cell patch-clamp technique was used to control membrane voltage. I(NCX) (identified as Ni2+ sensitive current) was recorded using a ramp clamp protocol under conditions to inhibit contaminating currents.


RESULTS
With 0.6 mM sevoflurane, outward I(NCX) at positive voltages (> or = 0 mV) and inward I(NCX) at voltages negative to -60 mV was significantly reduced (P<0.05, n=13; I(NCX) reduced by 48% at +50 and 65% of control at -120 mV). Halothane (0.6 mM) inhibited outward I(NCX) at voltages positive to -10 mV and inward I(NCX) at voltages negative to -80 mV (P<0.05, n=10; I(NCX) reduced by 64% at +50 and 65% of control at -120 mV). Anaesthetic-induced inhibition of both inward and outward current was not voltage-dependent.


CONCLUSIONS
Inhibition of Ca2+ efflux via NCX (i.e. inward I(NCX)) during an exposure to halothane or sevoflurane would be expected to limit the negative inotropic effects of these agents and help maintain SR Ca2+ content.
Bru-Mercier
G
G
School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK.
Hopkins
P M
PM
Harrison
S M
SM
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D006221:Halothane / Q000494:pharmacology*; D006352:Heart Ventricles / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008738:Methyl Ethers / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane; D019831:Sodium-Calcium Exchanger / Q000187:drug effects* / Q000378:metabolism
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D019831:Sodium-Calcium Exchanger; D000077149:Sevoflurane; D006221:Halothane