pH regulation of K+ efflux from myocytes in isolated rat hearts: Rb-87, Li-7, and P-31 NMR studies

This study investigates the effects of intracellular (pH(i)) and extracellu lar pH (pH(e)) on the efflux of Rb+ and Li+ in isolated rat hearts, Rb-87 a nd Li-7 NMR were used to measure Rb+ and Li+ content, respectively, of hear ts, and P-31 NMR was used to monitor pH(i), pH(e), and phosphate levels. Af ter 30-min equilibration with Rb+ or Li+, effluxes were initiated by switch ing perfusion to a Rb+- or Li+-free, high-K+ (20.7 mM) Krebs-Henseleit buff er with 15 mu M bumetanide. Monensin (2 mu M) increased pH(i) from 7.10 +/- 0.05 to 7.32 +/- 0.07 and resulted in activation of Rb+ efflux; the first- order rate constant (k x 10(3), in min(-1)) increased from 42 +/- 2 to 116 +/- 16. Glibenclamide (4 mu M) did not inhibit monensin-activated Rb+ efflu x (k = 110 +/- 17), whereas quinine (0.2 mM) slightly inhibited it by 19 +/ - 9%. Infusion of 15 mM NH4Cl during Rb+ washout increased k for Rb+ efflux by 93% (81 +/- 8), which was glibenclamide and quinine insensitive, and ca used a transient increase in pHi to 7.25 +/- 0.08. Intracellular Li+ inhibi ted NH4Cl-stimulated Rb+ efflux by 55%. Monensin and NH4Cl stimulated Li+ e fflux by 40%, increasing k from 29 +/- 3 to 43 +/- 7 and 41 +/- 3, respecti vely. The stimulation was not sensitive to 10 mu M dimethylamiloride. Intra cellular acidosis that resulted from the washout of NH4Cl (pH 6.86 +/- 0.2) slightly inhibited Rb+ efflux (k = 36 +/- 5), whereas NH4Cl itself in the absence of pH(i) changes did not markedly affect Rb+ efflux. A moderate inc rease in pH(i) (7.17 +/- 0.06) produced by washout of 15 mM 2,2-dimethylpro pionate (DMP)-Tris from hearts preequilibrated with DMP did not markedly af fect Rb+ efflux. Neither global alkalosis (pH(i) 7.4, pH(e) 7.55) nor acido sis (pH(i) approximate to pH(e) 6.8) produced by 3 mM Tris base or 5 mM MES , respectively, affected Rb+ emux. We suggest that intracellular alkalosis stimulates Rb+ (K+) and Li+ effluxes by activating a nonselective sarcolemm al K+ (Li+)/cation exchanger or a K+ (Li+)-anion symporter.