EARLY AFTER-DEPOLARIZATIONS INDUCED BY NORADRENALINE MAY BE INITIATEDBY CALCIUM RELEASED FROM SARCOPLASMIC-RETICULUM

We investigated the effect of 10(-8) M noradrenaline (NA) on [Ca2+](i) and electrical activity of single myocytes of guinea-pig ventricular myocardium loaded with Indo 1-AM. Membrane potential was recorded by m eans of the patch electrode and patch amplifier set to the current cla mp mode. Cells were stimulated at a rate of 30/min by 3 ms pulses of t he current injected through the recording electrode. Superfusion of NA resulted in slight shortening of action potentials (APs), increase in rate of rise and amplitude of the respective Ca2+ transients, and app earance of secondary Ca2+ transients of two kinds: 1. appearing before repolarisation of AP and decay of the preceding Ca2+ transient were c ompleted and 2. appearing between the APs. We named them early after-t ransients (EAT) and delayed after-transients (DAT), respectively. With out any additional intervention EATs caused some prolongation of APs d uration and DATs resulted in subthreshold delayed after-depolarisation s (DADs). When sarcolemmal K+ conductance was decreased by tetraethyla mmonium (TEA) in the patch electrode or 20 mu M BaCl2 in the Tyrode so lution, EATs initiated early after depolarizations (EADs) and DATs ini tiated suprathreshold DADs triggering full-sized APs. Superfusion of 3 0.0 mM Na+ (replaced with LiCl) resulted in reduction of AP duration b y similar to 70% and appearance of DATs. Also, the frequent multiple o scillations of Ca2+ concentration were often observed. Neither DATs no r the oscillations had any affect on electrical activity of the cells. Their electrogenicity could not be increased by TEA or 20.0 mu M Ba2. EATs and DATs and their respective EADs and DADs could not be initia ted by NA or low Na+ superfusion in the cells pretreated with 2 x 10(- 7) M thapsigargin, a selective blocker of Ca2+-ATPase of sarcoplasmic reticulum (SR). We conclude that in contrast to the current hypothesis , EADs can be initiated by Ca2+ released early in the cardiac cycle fr om the overloaded SR, and that electrogenicity of both types of Ca2+ o scillations critically depends on the sarcolemmal K+ conductance.