title: Effects of propofol and enflurane on action potentials, membrane currents and contraction of guinea-pig isolated ventricular myocytes.
abstract: 1. The effects of two general anaesthetics, propofol and enflurane, on electrical activity and contractions were investigated in single myocytes isolated from guinea-pig ventricles. 2. Propofol and enflurane depressed the plateau and shortened the duration of action potentials. 3. Under voltage-clamp conditions, propofol and enflurane reduced the amplitude of inward calcium current and of additional inward current activated by cytosolic calcium. 4. Contractions (measured with an optical technique) accompanying either action potentials or second inward currents (in response to depolarizations to 0 mV) were reduced by both anaesthetics. The mechanisms for calcium entry during contractions accompanying pulses to positive potentials such as +60 mV are thought to differ from those accompanying second inward currents which are evoked by pulses from -40 to 0 mV. Enflurane enhanced the amplitudes of contractions accompanying pulses to positive potentials; in contrast these contractions were depressed by propofol. 5. In experiments where recovery processes were investigated by use of pairs of voltage-clamp pulses with a variable interval between them, enflurane but not propofol slowed the recovery of contractions and calcium-activated 'tail' currents. These observations are consistent with the hypothesis that enflurane may impair calcium handling by the sarcoplasmic reticulum whereas propofol has little, if any, effect at this site. 6. In conclusion, the actions of propofol and enflurane on second inward currents contribute to their effects on action potentials and contraction. The negative inotropic effect of both anaesthetics may result partly from reduced calcium influx to trigger contraction, and for enflurane, partly from an impairment of calcium handling by the sarcoplasmic reticulum.
authors.affiliation: University Department of Pharmacology, Oxford.
authors.forename: R M
authors.initials: RM
authors.lastname: Puttick
authors.forename: D A
authors.initials: DA
authors.lastname: Terrar
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects*; D004737:Enflurane / Q000494:pharmacology*; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D015742:Propofol / Q000494:pharmacology*
chemical_list: D015220:Calcium Channels; D004737:Enflurane; D002118:Calcium; D015742:Propofol