Effects of propofol on a Ca2+-activated CI- current in rabbit ventricular myocytes.
Propofol is a widely used intravenous anesthetic, which is known to affect cardiac functions. Cardiac effects may be caused by direct actions on ion channels of the heart. While effects of propofol on several ion channels have been studied at the whole cell and single-channel levels, its effects, if any, on anion currents have yet to be examined. Effects of propofol on Ca2+-activated Cl- current (I(Cl(Ca))) were investigated in single myocytes isolated from rabbit ventricles by the whole-cell patch clamp technique at 36 degrees C. I(Cl(Ca)) was activated by perfusing internal solutions with 0.1 microM free Ca2+ in the absence and presence of 10 mM internal Na+, eliciting I(Ca)-dependent and -independent component, respectively. By the application of propofol (0.1-300 microM), I(Ca)-independent I(Cl(Ca)) was strongly inhibited in a dose-dependent manner with an IC50 of about 5 microM. The blocking effects of propofol were voltage independent. On the other hand, the I(Ca)-dependent component of I(Cl(Ca)) was little affected by propofol at concentrations of up to 50 microM. The outward Na+/Ca2+ exchanger current was also blocked by application of 5 microM propofol. We conclude that propofol inhibits cardiac I(Cl(Ca)) in rabbit ventricular myocytes, mainly the I(Ca)-independent component, at therapeutic concentrations. The inhibition may be due to block of a reverse mode of Na+/Ca2+ exchange current.
Asahina
T
T
Department of Dental Anesthesiology, Faculty of Dentistry, Tokyo Medical and Dental University, Japan.
Kawano
S
S
Umino
M
M
Hiraoka
M
M
D000200:Action Potentials; D000704:Analysis of Variance; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D015742:Propofol / Q000494:pharmacology*; D011817:Rabbits; D019831:Sodium-Calcium Exchanger / Q000187:drug effects*
D018686:Anesthetics, Intravenous; D015220:Calcium Channels; D019831:Sodium-Calcium Exchanger; D015742:Propofol