The intracellular sodium activity of cardiac Purkinje fibres during inhibition and re-activation of the Na-K pump.
1. The intracellular Na activity, aiNa, of sheep heart Purkinje fibres was continuously monitored using Na+-sensitive glass micro-electrodes. The effects of removal and restoration of external K, and of application and removal of various cardioactive steroids, were investigated. 2. The aiNa increased in K-free solutions and rapidly recovered on addition of external K. The rate of this recovery depended on both the external K concentration, [K]o, and the aiNa. The rate of aiNa recovery was found to be half maximally activated at a [K]o of about 10 mM. If corrections are applied to allow for changes in the net passive Na influx at various [K]o, then this value is increased to approximately 12.5 mM. 3. At a given [K]o, there appeared to be a linear relationship between the rate of aiNa recovery and the level to which aiNa had increased in K-free solution (over the range of aiNa from 7.5 to 31 mM). 4. Addition of the cardioactive steroids strophanthidin, acetylstrophanthidin, actodigin (AY 22,241) or dihydro-ouabain produced rapid changes of aiNa. At low concentrations, these compounds sometimes produced a small decrease in aiNa, while at concentrations above 10(-7) M they produced a dose-dependent increase. 5. The effects on aiNa of both low and high concentrations of all these cardioactive steroids were readily reversible within 120 min. The time course of the aiNa recovery mainly depended on the concentration of the cardioactive steroid applied, and on the level to which aiNa had increased. 6. Upon addition of a cardioactive steroid (above 10(-7) M, aiNa at first increased almost linearly with time. The rates of such an increase were measured during this period at various cardioactive steroid concentrations and used to produce dose-response curves. The concentrations that produced a half-maximum rate of aiNa increase were near to 10(-6) M for strophanthidin and acetylstrophanthidin, but near to 10(-5) M for actodigin and dihydro-ouabain. 7. The mean maximum rate of aiNa increase produced by the addition of a high cardioactive steroid concentration was 0.49 +/- 0.17 mM/min (+/-S.D., n = 21). This would indicate a net passive Na influx into the cells of approximately 2.8 p-mole/cm2sec. 8. This maximum rate of aiNa increase could be achieved by the addition of 10(-5) M-strophanthidin or acetylstrophanthidin, but 10(-4) to 10(-3) M-actodigin or dihydro-ouabain was required to produce a similar rate of increase. 9. The addition of these high cardioactive steroid concentrations produced an initially rapid increase of aiNa. After 15-30 min this aiNa increase slowed considerably. The aiNa appeared to reach a 'plateau' within 2-4 hr at levels much below those predicted for a Na electrochemical equilibrium across the cell membrane.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002298:Cardenolides / Q000494:pharmacology; D002301:Cardiac Glycosides / Q000494:pharmacology; D004071:Digitalis Glycosides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006329:Heart Conduction System / Q000378:metabolism*; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D007700:Kinetics; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology; D011690:Purkinje Fibers / Q000378:metabolism*; D012756:Sheep; D012964:Sodium / Q000378:metabolism*; D013327:Strophanthidin / Q000494:pharmacology
D002298:Cardenolides; D002301:Cardiac Glycosides; D004071:Digitalis Glycosides; D010042:Ouabain; D013327:Strophanthidin; D012964:Sodium; D011188:Potassium