Possible evidence for transmembrane K⁺-H⁺ exchange system in guinea pig myocardium

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 (0.3 mM) or dimethylamiloride (0.1 mM), 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 (0.3 mM) 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.