Slow recovery from inactivation of inward currents in mammalian myocardial fibres

Reactivation kinetics of the rapid and slow inward currents in ventricular fibres have been assessed by studying the maximum rate of rise ((dV/dt)max) of the action potential upstroke and the duration of the plateau in progressively earlier premature responses. Reactivation of the slow inward current was also studied by voltage clamp technique in sheep and pig ventricular trabeculae.2. The time constant of recovery of (dV/dt)max was voltage dependent and increased from less than 20 msec when the resting membrane potential was more negative than -80 mV to more than 100 msec when the resting membrane potential was between -65 and -60 mV. Similar results were obtained in Purkinje fibres. These results suggest that the time constant for reactivation is slower than the time constant for inactivation of the rapid inward current system by at least one order of magnitude.3. The time constant of recovery of plateau duration was also voltage dependent and increased from 30 to 70 msec as the membrane potential was changed from -85 to -60 mV.4. The reactivation time constant of the slow inward current determined by voltage clamp experiments were similar to the results obtained by analysis of plateau duration. At potentials less negative than -60 mV the time constant of reactivation became progressively longer. Unlike reactivation time constants of (dV/dt)max, the time constants of reactivation of the slow inward current were similar to the time constants of inactivation.5. Our results indicate that (a) in premature action potentials, time as well as voltage are important determinants of (dV/dt)max in myocardial and Purkinje fibres, (b) the kinetics of reactivation of the rapid inward current in cardiac fibres are different from those in nerve and (c) plateau duration of premature action potentials in ventricular myocardial fibres is largely determined by the kinetics of reactivation of the slow calcium inward current.