Slow recovery from inactivation of inward currents in mammalian myocardial fibres

Abstract

SUMMARY1. 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

Effects of disopyramide on the maximum rate of rise of action potential (Vmax) in guinea-pig papillary muscles.

“…Earliest component: The time constants of the earliest component (8-13 msec) estimated for the controls in 2.7, 5.4, and 8.1 mM [K+](, are of the same order of magnitude reported in previous studies using guinea-pig papillary muscles (6,8,9,17 In the absence of drugs, the slow recovery of the sodium system with a time constant of several hundred msec has been observed in sheep Purkinje fibers (19,20) and frog atrial preparations (21).…”

“…Effects of disopyramide on the recovery process of Vmah: The recovery process of Vmax may represent not only the reactivation of the sodium system from inactivation (17), but also the functional state of Na/K pump (18) and other changes in active and passive membrane properties. Further, Hondeghem and Katzung's model (7) suggests that there are several routes for the reactivation of the sodium channels from inactivation: one route for inactivated drug-free channels and two routes for inactivated drug-associated channels (For details, see diagram 1 in reference 7).…”

“…After an equilibration period of at least one hour, the transmembrane potential was recorded by means of a conventional microelectrode filled with 3 M KCI (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) The recovery process of Vmy, was examined in the following two ways: (i) the process within the basic stimulation interval of 1 sec (premature recovery) was studied by intro ducing premature test stimuli (2-3 times the intensity of the basic stimulus) in every 8-10 basic stimuli, (ii) the process beyond the basic stimulation interval (post-interruption recovery) was studied by assessing in the first response after interruption of the basic stimuli for various periods (2 sec to 10 min). The term "diastolic interval" is defined as the interval from the 90% repolarization time of the conditioning action potential to the onset of the test action potential.…”

Relationship between the effects of Goniopora toxin on action potential and on contractile force in guinea-pig papillary muscle.

“…In the present study using guinea-pig papillary muscle, the lengthened duration of the action potential was also shortened by TTX. The major effect of TTX in cardiac muscle is inhibition of the sodium current through the fast sodium channel (6), and in the normal state, the fast sodium channel of the cardiac muscle is rapidly activated and then rapidly inactivated upon depolarization (7,8). And it is reported that TTX does not affect the duration of the action potential in atrial and/ or ventricular muscle (9, 10) but only shortens that of the conducting system (10,11).…”

Effects of bepridil on the electrophysiological properties of guinea‐pig ventricular muscles

“…The recovery kinetics of V,1,, were determined by a method similar to that used by Gettes & Reuter (1974). The tissue was stimulated at a basal conditioning rate of 1.0Hz.…”