Kinetics of inactivation and recovery of the slow inward current in the mammalian ventricular myocardium.

In order to study the kinetics of inactivation and recovery of the slow inward current in the mammalian ventricular myocardium voltage clamp experiments using the double sucrose gap technique were performed on isolated trabeculae and papillary muscles of cats. The separation of the slow inward current from the fast Na current was achieved by use of the conditioning clamp procedure. 1. The decay of the Ca current reflects the inactivation which develops due to depolarization. The rate of inactivation depends upon the membrane potential. Excess Ca (8.8 mM) accelerates the inactivation speed indicating that Ca ions not only act as charge carrier of the slow inward current but might influence in addition the kinetics of the slow membrane channel. In the presence of a lowered temperature a deceleration of inactivation (Q10 2.3) occurs. 2 If the membrane is repolarized a recovery process takes place restoring the availability of the slow membrane channel. As the inactivation the recovery rate depends upon the membrane potential. Excess Ca causes an acceleration whereas a decrease in temperature diminishes the recovery speed (Q10 2.3). Consequently, the Ca supply to the myocardial cell can be modified not only by changes of the transmembrane Ca concentration gradient or by an alteration of the Ca conductance of the slow channel but also by changes in the degree of recovery after a preceding Ca current. 3. Compared with the inactivation the recovery proceeds very slowly. Assuming that this slow recovery represents an inherent kinetic feature of the slow channel the kinetics of inactivation and removal of inactivation are not describable by a single inactivation variable (called as f by Reuter, 1973) which is of the Hodgkin-Huxley type. If a second inactivation variable (called as l) would be introduced additionally a formulation of the inactivation-recovery process of the slow membrane channel on the basis of the Hodgkin-Huxley model becomes feasible.