Opposite effects of halothane on guinea-pig ventricular action potential duration.
Halothane protects the heart against the reperfusion injury observed after an ischemia. In ischemic or anoxic conditions, a large ATP-sensitive K(+) (K(ATP)) conductance is supposed to provide an endogenous protection to the myocardium. In this study, we tested the possibility that halothane acted by modulating this conductance. Isolated guinea-pig cardiomyocytes were successively studied in current clamp and in voltage-clamp conditions. Action potentials regulation by halothane was tested in control conditions and in situations where the K(ATP) channels were activated. In control conditions, halothane decreased action potential duration of myocytes but did not significantly alter the inward rectifying K(+) current. Conversely, halothane lengthened action potential of cells in which the K(ATP) conductance was activated, by inhibiting the K(ATP) current. In ischemic conditions, simultaneous shortening of long action potentials and lengthening of shortened ones would be expected to homogenize the absolute refractory period at the border between normoxic and anoxic zones. This effect, together with a decrease in calcium load, could protect the myocardium against re-entrant arrhythmias.
Terrenoire
C
C
CNRS UMR5578, Laboratoire de Physiologie des Eléments Excitables, Université Claude Bernard-Lyon1, F-69622, Villeurbanne, France.
Piriou
V
V
Bonvallet
R
R
Chouabe
C
C
Espinosa
L
L
Rougier
O
O
Tourneur
Y
Y
D000200:Action Potentials / Q000187:drug effects; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002839:Chromans / Q000494:pharmacology; D006168:Guinea Pigs; D006221:Halothane / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000819:agonists / Q000187:drug effects / Q000378:metabolism; D012032:Refractory Period, Electrophysiological / Q000187:drug effects
D018685:Anesthetics, Inhalation; D002839:Chromans; D015221:Potassium Channels; C092986:SR 47063; D006221:Halothane