Cesium Abolishes the Barium‐Induced Pacemaker Potential and Current in Guinea Pig Ventricular Myocytes

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Abstract
Cesium Abolishes Barium‐Induced PM Current. 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 If at the resting potential, this approach permits verification of whether Cs+ is a specific blocker of I, 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 us a function of time (no If or K+ depletion). Cesium (4mM) reduced the current size during the hyperpolarizing steps hut 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 the 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 Ikl channels were already blocked by Ba2+ and the time‐dependent changes induced by Ba2+ 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, Cs+ abolishes the Ba2+‐induced pacemaker current by blocking the time‐dependent change in K+ conductance, not by blocking If. 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 If