Dependence of Na+ pump current on external monovalent cations and membrane potential in rabbit cardiac Purkinje cells.

1. The effect of membrane potential and various extracellular monovalent cations on the Na+ pump current (Ip) was studied on isolated, single Purkinje cells of the rabbit heart by means of whole‐cell recording. 2. Ip was identified as current activated by external K+ or its congeners NH4+ and Tl+. The current was blocked by dihydroouabain (1‐5 x 10(‐4) M) over the whole range of membrane potentials tested. 3. In Na(+)‐containing solution half‐maximum Ip activation (K0.5) occurred at 0.4 mM‐Tl+, 1.9 mM‐K+ and 5.7 mM‐NH4+ (holding potential, ‐20 mV). 4. The pump current (Ip)‐voltage (V) relationship of the cells in Na(+)‐containing media with K+ or its congeners at the tested concentrations greater than K0.5 displayed a steep positive slope at negative membrane potentials between ‐120 and ‐20 mV. Little voltage dependence of Ip was observed at more positive potentials up to +40 mV. At even more positive potentials Ip measured at 2 and 5.4 mM‐K+ decreased. 5. Lowering the concentration of K+ or its congeners below the K0.5 value in Na(+)‐containing solution induced a region of negative slope of the Ip‐V curve at membrane potentials positive to ‐20 mV. 6. The shape of the Ip‐V relationship remained unchanged when the K+ concentration (5.4 mM) of the Na(+)‐containing medium was replaced by NH4+ or Tl+ concentrations of similar potency to activate Ip (20 mM‐NH4+ or 2 mM‐Tl+). 7. In Na(+)‐free, choline‐containing solution half‐maximum Ip activation occurred at 0.13 mM‐K+ (holding potential, ‐20 mV). 8. At negative membrane potentials the positive slope of the Ip‐V curve was flatter in Na(+)‐free than in Na(+)‐containing media. A reduced voltage dependence of Ip persisted, regardless of whether choline ions or Li+ were used as a Na+ substitute. 9. Lowering the K+ concentration of the Na(+)‐free, choline‐containing solution to 0.05 mM evoked an extended region of negative slope in the Ip‐V relationship at membrane potentials between ‐40 and +60 mV. 10. It is concluded that the apparent affinity of the Na(+)‐K+ pump towards K+ in cardiac Purkinje cells depends on both the membrane potential and the extracellular Na+ concentration. 11. The region of negative slope of the Ip‐V curve observed in cells which were superfused with media containing low concentrations of K+ or its congeners strongly suggests the existence of at least two voltage‐sensitive steps in the cardiac Na(+)‐K+ pump cycle.(ABSTRACT TRUNCATED AT 400 WORDS)