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

Abstract

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.

Ionic currents during hypoxia in voltage-clamped cat ventricular muscle.

“…The curve relating Tf to potential in the range between -40 and +40 mV was comparable to the curves obtained by New and Trautwein (1972) and Kohlhardt et al (1975) in the same preparation. One should realize that the inverse bell shape of the curve probably results from two artefacts: the interference of a rather slow activation process with inactivation near threshold (Trautwein et al, 1975) and an important degree of activation of time-dependent outward current at positive potentials (McDonald and Trautwein, 1978b).…”

Spontaneous Electrical Activity Induced by Depolarizing Currents in Canine Ventricular Myocardium

“…The shortening of cardiac action potentials in high Ca++ media is well known, and the mechanism for the shortening in the spontaneous AP's should be the same as that responsible for shortening of driven AP's. 9) In proportion to the increase of firing rate, (dv/dt)max of the AP's was also increased with increasing [Ca++]. It should be emphasized here that (dv/dt)max for different [Ca++] must be compared using the same takeoff potentials but not using the same applied currents since small changes in depolarization level per se dramatically affected the value of (dv/dt)max.…”

Calcium conductance in relation to contractility in frog myocardium.

“…The considerable variations in published data on the time-and voltagedependence of Ca inactivation (Beeler & Reuter, 1970a;New & Trautwein, 1972;Besseau, 1972;Kohlhardt, Krause, Kubler & Herdey, 1975) could be accounted for by the use of different methods for estimating pure Ca current, and the difficulty of separating this from the other membrane currents. In this study our indirect approach using phasic tension measurements as an indicator of Ca kinetics avoided such difficulties and its validity is supported by the close relation between calcium current and phasic tension.…”