Actions of barium and rubidium on membrane currents in canine Purkinje fibres.

Abstract

SUMMARY1. 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.2. 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.3. 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.4. 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.5. 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.6. 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-dqpendent, and possibly voltage-dependent manner. Also, the presence of a slow component of pace-maker

Effects of sodium‐potassium pump inhibition and low sodium on membrane potential in cultured embryonic chick heart cells.

“…The same argument applies to Ba2+ which, like Cs+, caused a decrease in hyperpolarization despite the fact that it is a blocker of PK (Cohen et al 1983;DiFrancesco et al 1984) and does not attenuate Na+-Ca2+ exchange in cultured chick heart cells under conditions similar to those reported here (Jacob et al 1986). …”

“…Cohen et al 1983) and at 1 mM it significantly (P < 0-0005) reduced the low-[Na+]0 hyperpolarization from 39-0+06 mV (n = 3) to 31-3±+0-7 mV (n = 3). The significance of this is obscured by the fact that Ba2+ has been reported to block Na+<Ca2+ exchange (Trosper &;Philipson, 1983).…”

Isoprenaline, Ca2+ and the Na(+)‐K+ pump in guinea‐pig ventricular myocytes.

“…As will be shown later in the results, reducing [Na+]i to a more physiological 6 mm does not alter the experimental outcome. We also put 0 5 mM-Ba2+ in the bath to block the majority of the K+ conductance (Cohen et al 1983), thus minimizing accumulation/depletion of K+ in the T-system of the myocytes. We estimate that changes in T-system K+ concentration are less than 0-1 mM.…”

Pacemaker current in single cells and in aggregates of cells dissociated from the embryonic chick heart.

“…The latter group has also emphasized the contribution of IK time dependence to pacemaker current waveforms. This mechanism offers an alternative explanation for the marked effect of Ba2± on pacemaker currents in multicellular preparations, such as heart cell aggregates and canine cardiac Purkinje fibres, in which ion accumulation and depletion are believed to be considerably less pronounced than in sheep cardiac Purkinje fibres (Clay et al 1979;Cohen, Falk & Mulrine, 1983).…”