Effects of pH on Na+-Ca2+ exchange in canine cardiac sarcolemmal vesicles.
Using highly purified sarcolemmal vesicles isolated from dog ventricles, we examined the effects of pH on Na+-Ca2+ exchange. The initial rate of Nai+-dependent Ca2+ uptake is a sigmoid function of pH. The Ca2+ uptake is inhibited at pH 6 and stimulated at pH 9 (as compared with uptake at pH 7.4). This dependence on pH suggests that the ionization state of a histidine residue may be important in Na+-Ca2+ exchange. The effects of H+ on Nai+-dependent Ca2+ uptake are partially competitive with Ca2+, although this relationship is complex. Nao+-dependent Ca2+ efflux is also sensitive to H+ and increases monotonically with pH. These effects of pH appear to be due to intrinsic interactions with the Na+-Ca2+ exchange system and are not due to an alteration of Na+-H+ exchange or membrane permeability. The effects of pH on vesicular Na+-Ca2+ exchange are apparent only at low Ca2+ and Na+ concentrations. Thus modulation of vesicular Na+-Ca2+ exchange by pH is manifest only under ionic conditions which exist intracellularly in intact myocardium. Since the negative inotropy caused by acidosis is thought to reflect a fall in internal pH, these results suggest that alteration of sarcolemmal Ca2+ transport (medicated by Na+-Ca2+ exchange) by internal pH may contribute to the regulation of myocardial contractility by pH.
D000818:Animals; D001692:Biological Transport; D002021:Buffers; D002118:Calcium / Q000378:metabolism*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D009206:Myocardium / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D012508:Sarcolemma / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013395:Sucrose / Q000494:pharmacology; D014634:Valinomycin / Q000494:pharmacology
D002021:Buffers; D014634:Valinomycin; D013395:Sucrose; D011189:Potassium Chloride; D012964:Sodium; D002118:Calcium