THE PACEMAKER CURRENT IN CARDIAC PURKINJE MYOCYTES

It is generally assumed that in cardiac Purkinje fibers the hyperpolar ization activated inward current if underlies the pacemaker potential. Because some findings are at odds with this interpretation, we used t he whole cell patch clamp method to study the currents in the voltage range of diastolic depolarization in single canine Purkinje myocytes, a preparation where many confounding limitations can be avoided. In Ty rode solution ([K+](o) = 5.4 mM), hyperpolarizing steps from V-h = -50 mV resulted in a time-dependent inwardly increasing current in the vo ltage range of diastolic depolarization. This time-dependent current ( i(kdd)) appeared around -60 mV and reversed near E(K). Small superimpo sed hyperpolarizing steps (5 mV) applied during the voltage clamp step showed that the slope conductance decreases during the development of this time-dependent current. Decreasing [K+](o) from 5.4 to 2.7 mM sh ifted the reversal potential to a more negative value, near the corres ponding E(K). Increasing [K+](o) to 10.8 mM almost abolished i(kdd) Cs + (2 mM) markedly reduced or blocked the time-dependent current at pot entials positive and negative to E(K). Ba2+ (4 mM) abolished the time- dependent current in its usual range of potentials and unmasked anothe r time-dependent current (presumably i(f)) with a threshold of similar to-90 mV (>20 mV negative to that of the time-dependent current in Ty rode solution). During more negative steps, i(f) increased in size and did not reverse. During i(f), the slope conductance measured with sma ll (8-10 mV) superimposed clamp steps increased. High [K+](o) (10.8 mM ) markedly increased and Cs+ (2 mM) blocked i(f). We conclude that: (a ) in the absence of Ba2+, a time-dependent current does reverse near E (K) and its reversal is unrelated to K+ depletion; (b) the slope condu ctance of that time-dependent current decreases in the absence of K+ d epletion at potentials positive to E(K) where inactivation of i(K1) is unlikely to occur. (c) Ba2+ blocks this time-dependent current and un masks another time-dependent current (i(f)) with a more negative (>20 mV) threshold and no reversal at more negative values; (d) Cst blocks both time-dependent currents recorded in the absence and presence of B a2+. The data suggest that in the diastolic range of potentials in Pur kinje myocytes there is a voltage- and time-dependent K+ current (i(kd d)) that can be separated from the hyperpolarization-activated inward current i(f).