Influence of external barium and potassium on potassium efflux in depolarized frog sartorius muscles

Abstract

Efflux of 42K+ was measured in frog sartorius muscles equilibrated in depolarizing solutions with external K+ concentrations [( K+]0) between 75 and 300 mM and NaCl concentrations of 60, 120, or 240 mM. For several combinations of KCl and NaCl, steady-state internal potentials (Vi) were the same for different [K+]0. For the range of Vi examined, K+ efflux occurs principally through the K+ inward rectifier channels. When external K+ is removed Vi remains constant for 2 to 3 hr because of the high membrane conductance to Cl-, but K+ efflux drops by about one order of magnitude. External Ba2+ in the presence or absence of external K+ produces an inhibition of K+ efflux described by a relation of the form u = (u1/(1 + C [Ba2+]0] + u2, where u is the uninhibited fraction of K+ efflux; u1, u2 and C are constants; and u1 + u2 = 1. C depends both on [K+]0 and Vi. When [K+]0 greater than or equal to 75 mM, increasing [K+]0 at constant Vi reduces Ba2+ sensitivity. For constant Vi greater than or equal to -30 mV, Ba2+ sensitivity is less when [K+]0 = 0 than when [K+]0 greater than or equal to 75 mM. When [K+]0 = 0, Ba2+ sensitivity decreases as Vi is made more positive. The dependence of the Ba2+ sensitivity on Vi at constant [K+]0 is greater when [K+]0 = 0 than when [K+]0 greater than or equal to 75 mM. Both the activation of K+ efflux by external K+ and the Ba2+ inhibition of K+ efflux can be explained on the basis of two membrane control sites associated with each channel. When both sites are occupied by K+, the channels are in a high flux state. When one or both sites are empty, the channels are in a low, nonzero flux state. When Ba2+ occupies either site, K+ efflux is further reduced. The reduction of Ba2+-sensitivity by increasing [K+]0 at high [K+]0 is attributable to the displacement of Ba2+ from the control sites by K+. The increased Ba2+ sensitivity produced by going from [K+]0 = 0 to [K+] greater than or equal to 75 mM when Vi greater than or equal to -30 mV is attributable to states in which Ba2+ occupies one site and K+ the other when [K+]0 not equal to 0.(ABSTRACT TRUNCATED AT 400 WORDS)

Paradoxical depolarization of BA2+‐ treated muscle exposed to low extracellular K+: Insights into resting potential abnormalities in hypokalemic paralysis

“…A residual inward current with linear voltage-dependence, the "leak", was observed at potentials less than Ϫ60 mV after Ba . 24,[52][53][54] In our preparation, the reversal potential of the Ba 2ϩ -sensitive current is Ϫ87 mV, slightly depolarized from E K (Ϫ96 mV, based on a presumed internal K ϩ concentration of ϳ150 mM). This discrepancy may reflect nonideal ionic selectivity for K ϩ over other ions in the setting of physiological ion concentrations (for instance, some IRK channels exhibit low permeability to Ca 2ϩ in low external K ϩ ), 13 or possibly the admixture of additional ionic currents through other channels.…”

“…16,47 The toxic effect of Ba 2ϩ is thought to be due to its high-affinity block of IRK channels. [52][53][54] Using excised fibers exposed to different concentrations of Ba 2ϩ , we generated experimental support for the notion that the decoupling of V REST from E K under conditions of depleted extracellular K ϩ is indeed a consequence of reduction of the IRK conductance, and that this threshold can be potentiated by partial block of IRK currents. Computer simulations based on these data demonstrate how V REST responds to challenges with low extracellular K ϩ , and how derangements of this response can predispose to aberrant depolarization.…”

Zinc inhibition of chloride efflux from skeletal muscle ofRana pipiens and its modification by external pH and chloride activity

“…When muscles are equilibrated in either 75 K+/60 Na + solution or in 150 K+/240 Na + solution the internal potential is -22 mV (Spalding, Swift & Horowicz, 1986). The ratio of C1-concentrations, [C1-], for these two solutions is 2.73 and the ratio of the C1-activities, (Cl-), is 2.59 (see Appendix B).…”

“…One purpose for using high-KC1 equilibrating solutions is that the internal potential of the fibers equals both the chloride and potassium equilibrium potential (Hodgkin & Horowicz, 1959;Spalding et al, 1986). Using standard 3 M KCl-filled glass microelectrode impalement techniques we measured the internal potential of sartorius muscle fibers in high-KCl solutions.…”

Zinc inhibition of potassium efflux in depolarized frog muscle and its modification by external hydrogen ions and diethylpyrocarbonate treatment

“…In these experiments, 42K+ efflux from sartorius muscles from the frog Rana pipiens was measured using the procedures described in the preceding paper (Spalding, Swift & Horowicz, 1986). K + effiux was calculated as the fraction of radioactive potassium lost from the muscle, expressed as an apparent effiux rate coefficient, k, and referred to simply as "K + efflux" with the units of rain -1.…”