CESIUM ABOLISHES THE BARIUM-INDUCED PACEMAKER POTENTIAL AND CURRENT IN GUINEA-PIG VENTRICULAR MYOCYTES

Introduction: The ability of cesium to block barium-induced diastolic depolarization (''Ba-DD'') and pacemaker current was tested in isolated ventricular myocytes, Because Ba-DD is due to decreasing K+ conductance and there is no I-f at the resting potential, this approach permits verification of whether Cs+ is a specific blocker of l(f) or if it instead also blocks a K+ pacemaker current. Methods and Results: Guinea pig isolated ventricular myocytes were studied by a discontinuous, single electrode, voltage clamp method, During hyperpolarizing voltage clamp steps from -80 up to -140 mV in Tyrode's solution, the inward current increased as a function of voltage but did not change as a function of time (no I-f or K+ depletion). Cesium (4 mM) reduced the current size during the hyperpolarizing steps but did not induce or unmask time-dependent currents, Barium (0.05 to 0.1 mM) induced diastolic depolarization, and, in its presence, depolarizing voltage clamp steps were followed by an outward tail current that reversed at -92.0 +/- 1.3 mV. Outward tail currents were larger at -50 mV than at the resting potential, and inward tail currents decayed more rapidly and to a larger extent during larger hyperpolarizing steps, In the presence of Ba2(+), Cs-+ (4 mM) had little effect on the steady-state current but markedly reduced or abolished undershoot, Ba-DD, and time-dependent tail currents at potentials both positive and negative to tbe resting potential, Cs+ had a smaller effect on the steady-state current-voltage (I-V) relation in the presence than in the absence of Ba2(+), as part of the I-K1, channels were already blocked by Ba2+ and the time-dependent changes induced by Ba-2+ were not present, Both Ba2+ and Cs+ had little blocking effect on the steady-state current positive to the negative slope region of the I-V relation. Conclusion: In ventricular myocytes, Csi abolishes the Ba2+-induced pacemaker current by blocking the time-dependent change in K+ conductance, not by blocking I-f. Because Cs+ can also block a decaying K+ pacemaker current, the abolition of a pacemaker current by Cs-+ in other cardiac tissues cannot be taken as unequivocal proof that the blocked current is I-f.