Ca-movement controlling myocardial contractility. I. Voltage-, current- and time-dependence of mechanical activity under voltage clamp conditions (cat papillary muscles and trabeculae).

Abstract

1. Tension development and membrane currents have been measured in cat ventricular fibres applying a double sucrose-gap voltage clamp technique. 2. A well defined mechanical threshold was found at which a considerable all-or-non response occurred. This threshold obviously coincided with the threshold potential of the fast inward current (INa). Changes in [Cae] (0.8–7.5 mM) did not separate the two thresholds. Ramp clamps of decreasing steepness shifted the threshold of bothINa and that of tension development towards less negative potentials. Ramp clamps ineffective in elicitingINa did not produce phasic tension development. This suggests that a fast inward current normally triggers the internal Ca release. 3. In rhythmically activated preparations the steady state voltage-tension relationship rose roughly in parallel toICa in a S-shaped manner up to about zero potential. With further depolarizations the steady-state tension development tended to decline again. It was concluded that this voltage dependent gain of contractile activation reflects the time integral of transmembrane Ca supply provided from the extracellular space. 4. Under steady state conditions peak tension produced by square clamps of a given suprathreshold voltage rose with prolongation of the clamp duration up to a maximum at 500–700 msec. This maximum in turn depended on the clamp potential applied. From the results obtained, a tension-time-voltage relationship has been drawn. Even under very long lasting depolarizations (up to 10 sec) usually no tonic responses occurred. 5. A muscle once activated by a suprathreshold square clamp did not respond to a second depolarization unless the membrane had been repolarized to a given level and for a given duration. The amplitude of contractile response to second clamp steps depended in a characteristic manner on both the voltage and the duration of the recovery period. 6. Mechanical transients typically observed when either the voltage or the duration of clamp steps had been changed were analyzed in order to obtain information about the kinetics of intracellular Ca movements assumed to take place in a multicompartment model derived from structural and functional observations.