title: The effects of halothane, isoflurane, and sevoflurane on Ca2+ current and transient outward K+ current in subendocardial and subepicardial myocytes from the rat left ventricle.
abstract: Halothane, isoflurane, and sevoflurane abbreviate ventricular action potential duration (APD), and for halothane this effect is greater in the subendocardium than in the subepicardium. In this study we investigated mechanisms underlying the regional effects of these anesthetics on APD. The effect of 0.6 mM halothane, isoflurane, and sevoflurane on the action potential, L-type Ca(2+) current, transient outward K(+) current (I(to)), and steady-state current was recorded in rat left ventricular subendocardial and subepicardial myocytes. Halothane and isoflurane (but not sevoflurane) reduced APD significantly (P < 0.05), more in subendocardial than subepicardial myocytes. Peak L-type Ca(2+) current did not differ between regions and, compared with control, was reduced significantly in both regions by 40% (P < 0.001), 20% (P < 0.001), and 12% (P < 0.01) by halothane, isoflurane, and sevoflurane, respectively. I(to) was greater in subepicardial (3.95 +/- 0.29 nA) than subendocardial (1.12 +/- 0.05 nA) myocytes. In subepicardial myocytes, peak I(to) was reduced significantly by halothane (P < 0.01) and isoflurane (P < 0.05) (by 8% and 7%, respectively) but was unaffected by sevoflurane. No significant reduction of I(to) was observed in subendocardial myocytes with the three anesthetics. The steady-state current was increased significantly (P < 0.05), but the extent of this increase did not differ between the two regions or among the three anesthetics. Therefore, greater inhibition of I(to) in subepicardial than subendocardial myocytes by halothane and isoflurane could underlie their transmural effects on APD.
authors.affiliation: *School of Biomedical Sciences and †Academic Unit of Anaesthesia, University of Leeds, Leeds, United Kingdom.
authors.forename: Amber
authors.initials: A
authors.lastname: Rithalia
authors.forename: Philip M
authors.initials: PM
authors.lastname: Hopkins
authors.forename: Simon M
authors.initials: SM
authors.lastname: Harrison
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D018685:Anesthetics, Inhalation; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D004594:Electrophysiology; D004699:Endocardium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006221:Halothane; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007530:Isoflurane; D007700:Kinetics; D008738:Methyl Ethers; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010496:Pericardium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D015220:Calcium Channels; D008738:Methyl Ethers; D015221:Potassium Channels; D000077149:Sevoflurane; D007530:Isoflurane; D006221:Halothane