Cesium abolishes the barium-induced pacemaker potential and current in guinea pig ventricular myocytes.
BACKGROUND
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 i(f) or if it instead also blocks a K+ pacemaker current.


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 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 IK1 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.


CONCLUSIONS
In ventricular myocytes, Cs+ abolishes the Ba(2+)-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).
Shen
J B
JB
Department of Physiology, State University of New York, Health Science Center, Brooklyn 11203.
Vassalle
M
M
D000818:Animals; D001464:Barium / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002586:Cesium / Q000378:metabolism / Q000494:pharmacology*; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011690:Purkinje Fibers / Q000187:drug effects*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism
D002586:Cesium; D001464:Barium; D000254:Sodium-Potassium-Exchanging ATPase