| Abstract: | The mechanism of electrical restitution was studied in isolated rat ventricular muscle using drugs that inhibit specific ion currents. The effect of transient changes in cytosolic Ca concentration and Na/Ca exchange in relation to the restitution process was also studied in single ventricular cardiomyocytes. Conventional microelectrode techniques were applied to record action potentials having gradually increasing coupling intervals, each evoked following a train of stimuli with a frequency of 1 Hz. Ion currents were recorded from enzymatically isolated cells using the whole cell patch clamp technique. Ca transients were monitored in myocytes loaded with the fluorescent dye, indo-1. The electrical restitution process in multicellular rat ventricular preparations at 37 °C was described as a sum of three exponential components: an early positive component, a subsequent fast negative component and a late negative component, having time constants of 21.9±1.9, 73.1±6.0 and 1053±61 ms, respectively (n=9). Inhibition of the transient outward K current, the delayed rectifier K current, or the chloride current did not substantially alter these time constants. The early positive and fast negative components were fully abolished by nifedipine or MnCl2. In the presence of caffeine, the fast negative component was absent, while the time constant of the early positive component increased to 39.5±5.8 ms (n=5). In single myocytes loaded with indo-1, the Ca transients decayed with a time constant of 151±12 ms at room temperature (n=5). These Ca transients were accompanied by inward current tails, identified as a Na/Ca exchange current, having a decay time constant of 140±4.5 ms. It is concluded that electrical restitution in rat ventricular muscle is relatively little affected by recovery from voltage-dependent inactivation of ion channels, it is rather governed by transient changes in cytosolic Ca concentration possible via Ca-dependent inactivation of the L-type Ca current and activation of the Na/Ca exchange current. |
