The aim of this study was to obtain evidence for a transmembrane K+-H+ exch
ange system in Langendorff-perfused whole hearts and isolated ventricular m
yocytes of guinea pig. Effluent relation between K+ and pH in the whole hea
rts perfused with HEPES-buffered Tyrode's solution indicated a significant
(p < 0.05) functional coupling of K+ uptake and H+ extrusion that was energ
y-dependent and omeprazole (OPZ)-sensitive. Administration of OPZ (0.3 mM)
or dimethylamiloride (0.1 mM), an inhibitor of Na+-H+ antiport, to whole he
arts subjected to the repetitive NH4Cl applications implied that both Na+-H
+ and putative K+-H+ countertransports contribute to the regulation of intr
acellular 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 ag
ent in the presence of K+. OPZ-induced inhibition of the putative K+-H+ exc
hanger likely resulted in subsarcolemmal acidification which was responsibl
e for the rate-independent suppression of I-Ca. In conclusion, these data p
rovide functional evidence for a myocardial transmembrane K+-H+ exchanger.