Effects of halothane on membrane potential, Ca²⁺ current and intracellular cAMP content in single guinea pig ventricular myocytes

In order to assess directly the actions of halothane on myocardium, especially on the Ca²⁺ channel we studied effects of halothane on electrophysiological and biochemical properties in single ventricular myocytes isolated enzymatically from guinea pig hearts. Membrane potentials and the slow inward Ca²⁺ current (I(ca)) were recorded with a suction microelectrode technique and a whole cell voltage clamp tecnhnique. The plateau duration of the action potential, maintained by I(Ca), AND I(Ca) was depressed by 2% halothane (to 58% and 29% of control respectively). To define the site on which halothane acts in the cell membrane, we measured cyclic adenosine monophosphate (cAMP) content of single ventricular myocytes using radioimmunoassay. One percent (1%) and 2% halothane directly produced a dose-dependent decrease in myocardial cAMP content (79% and 65% of control respectively). In conclusion, the present results suggest that the decrease of I(Ca) by halothane participates in the observed depression of the action potential plateau phase and demonstrate that halothane depression of I(Ca) is in part due to an inactivation of phosphorylation dependent gate in the Ca²⁺ channel resulting from the decrease in cAMP content by halothane.