Ionic mechanisms mediating the differential effects of methohexital and Thiopental on action potential duration in guinea pig and rabbit isolated ventricular myocytes

• Published in: Anesthesiology (Philadelphia) 1999, Vol.90 (1), p.156-164
• Main Authors: MARTYNYUK, A. E, MOREY, T. E, RAATIKAINEN, M. J. P, SEUBERT, C. N, DENNIS, D. M
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Anesthetics, Intravenous - pharmacology; Anesthetics. Neuromuscular blocking agents; Animals; Biological and medical sciences; Calcium Channels - drug effects; Delayed Rectifier Potassium Channels; Electric Stimulation; Female; Guinea Pigs; Heart - drug effects; Heart - physiology; Heart Ventricles - cytology; Heart Ventricles - drug effects; In Vitro Techniques; Ion Channel Gating; Male; Medical sciences; Methohexital - pharmacology; Myocardium - cytology; Neuropharmacology; Patch-Clamp Techniques; Pharmacology. Drug treatments; Potassium Channels - drug effects; Potassium Channels, Inwardly Rectifying; Potassium Channels, Voltage-Gated; Rabbits; Thiopental - pharmacology
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/00000542-199901000-00021

Commonly used barbiturate anesthetics may significantly influence cardiac electrophysiologic characteristics. The authors evaluated thiopental (a thiobarbiturate) and methohexital (an oxybarbiturate), two compounds with similar physicochemical properties but different structures, to determine whether they have distinct effects on the major ionic currents that determine action potential duration (APD) in ventricular myocytes. The effects of thiopental and methohexital (50 microM) on APD at 50% (APD50) and 90% (APD90) repolarization were studied in guinea pig and rabbit single ventricular myocytes using the patch-clamp technique in a whole-cell configuration. The ionic mechanisms underlying the APD changes were evaluated by measuring the anesthetics' effects on the L-type calcium inward current, the inward rectifier potassium current, and the delayed rectifier potassium current in guinea pig cells and on the transient outward potassium current in rabbit cells. Thiopental and methohexital caused opposite effects on APD. Whereas thiopental prolonged APD50 and APD90 in guinea pig and rabbit ventricular myocytes, methohexital shortened them. Thiopental markedly depressed both the inward and outward components of the inward rectifier potassium current, whereas methohexital caused minimal inhibition of the inward component and no change in the outward component. The delayed rectifier potassium current was inhibited by thiopental but significantly potentiated by methohexital. Neither thiopental nor methohexital significantly affected the transient outward potassium current or the L-type calcium inward current. Despite their similar lipid solubilities, molecular weights, and pKa values, thiopental increased and methohexital decreased the APD in ventricular myocytes by predominantly inhibiting the inward rectifier potassium current and the delayed rectifier potassium current and by increasing the delayed rectifier potassium current, respectively. These characteristics suggest distinct structure-specific actions of barbiturates on the function of myocardial ionic channels.