Possible Evidence for Transmembrane K⁺-H⁺ Exchange System in Guinea Pig Myocardium

抄録

The aim of this study was to obtain evidence for a transmembrane K⁺-H⁺ exchange system in Langendorff-perfused whole hearts and isolated ventricular myocytes of guinea pig. Effluent relation between K⁺ and pH in the whole hearts perfused with HEPES-buffered Tyrode's solution indicated a significant (p<0.05) functional coupling of K⁺ uptake and H⁺ extrusion that was energy-dependent and omeprazole (OPZ)-sensitive. Administration of OPZ (0.3mM) or dimethylamiloride (0.1mM), an inhibitor of Na⁺-H⁺ antiport, to whole hearts subjected to the repetitive NH₄Cl applications implied that both Na⁺-H⁺ and putative K⁺-H⁺ countertransports contribute to the regulation of intracellular pH. In isolated myocytes, voltage-dependent L-type Ca current (I_Ca) was inhibited by OPZ (0.3mM) under K⁺- and Na⁺-free condition by 11 to 14%, and was inhibited to a greater extent (i.e., by 36 to 40%) by this agent in the presence of K⁺. OPZ-induced inhibition of the putative K⁺-H⁺ exchanger likely resulted in subsarcolemmal acidification which was responsible for the rate-independent suppression of I_Ca. In conclusion, these data provide functional evidence for a myocardial transmembrane K⁺-H⁺ exchanger.