Actions of barium and rubidium on membrane currents in canine Purkinje fibres.
The actions of Ba2+ and Rb+, two blockers of background K+ conductance, were investigated. Recent studies performed on ungulate Purkinje fibres have suggested that the pace-maker current is an inward current activated by hyperpolarization. This hypothesis is based on the assumption that Ba2+ reduces the inwardly rectifying background K+ conductance without affecting the pace-maker current. Addition of 5 mM-BaCl2 to the bathing Tyrode solution decreases background K+ permeability and eliminates the reversal of the pace-maker current. The reversal reappears on return to Ba2+-free Tyrode solution. 5 mM-BaCl2 also reduces the time-dependent current at pace-maker potentials positive to about -95 mV in 4 mM-K+ Tyrode solution. The pace-maker current in Ba2+ Tyrode solution usually does not have an exponential time course, and often decays non-monotonically. It can take more than two minutes to reach a steady state. The fast initial component of membrane current, which is observed on hyperpolarizing in the pace-maker potential range in Purkinje fibres and which has been called the 'depletion current', is still present in Ba2+ Tyrode solution, but is reduced or eliminated if 10 mM-CsCl is added to the Ba2+ Tyrode solution. The addition of Cs+ is accompanied by an outward shift in membrane current in Ba2+ Tyrode solution. Ba2+ reduces the background K+ permeability in a dose-dependent manner. Addition of between 0.5 and 1 mM-BaCl2 achieves a maximum effect. Raising the amount of BaCl2 above this level reduces the time-dependent current even when no further effect on background permeability is observed. Rb+ substitution for K+ reduces the magnitude of the pace-maker current at potentials positive to -100 mV, eliminates the reversal of the pace-maker current, shifts the activation range to more negative potentials, and decreases the voltage dependence of pace-maker current kinetics. Rb+ addition to Tyrode solution has little effect on pace-maker current magnitude or time course positive to -90 mV, but does shift the reversal to more negative potentials. The available evidence suggests that the pace-maker current in Ba2+ Tyrode solution is an inward current activated by hyperpolarization. However, Ba2+ blocks an unknown fraction of the pace-maker current in a dose-dependent, and possibly voltage-dependent manner. Also, the presence of a slow component of pace-maker decay suggests that the standard Hodgkin-Huxley formalism for the analysis of pace-maker currents is inappropriate.
D000200:Action Potentials; D000818:Animals; D001464:Barium / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002586:Cesium / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D011690:Purkinje Fibers / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D012413:Rubidium / Q000494:pharmacology*
D002586:Cesium; D001464:Barium; D012413:Rubidium; D011188:Potassium