Reduction of the slow inward current of isolated rat ventricular cells by thiamylal and halothane

Abstract

The barbiturates and halothane exert a negative inotropic effect on the myocardium. A reduction in the slow inward current, carried mainly by calcium ions, is an important factor for the underlying mechanism because the calcium current during the action potential provides the calcium ions for accompanying contraction, supplies Ca ions to the sarcoplasmic reticulum for subsequent contractions, and induces Ca release from the store site. It has been suggested that reduction in the slow inward current caused by anesthetics is indicated by depression of the slow action potential of the partially depolarized myocardium. In order to assess directly the effect of anesthetics on the slow inward current, we carried out voltage clamp experiments with single isolated rat ventricular cells obtained by an enzymatic dissociation method. Thiamylal (10(-4) mol . l-1) and halothane (1%) decreased the slow inward current to 60 +/- 5% (mean +/- s.d., n = 8) and to 65 +/- 10% (mean +/- s.d., n = 8) of the control value, respectively, without changing the configuration of the current-voltage curve. The results provide further evidence for anesthetic reduction of the slow inward current of the myocardium, and suggest that the negative inotropic effect is at least partly due to the reduction in that current.