Several Ca2+ channel antagonists were shown to inhibit glibenclamide-sensitive K+ currents in follicle-enclosed Xenopus oocytes. We have investigated the stereoselectivity of the effects of Ca2+ channel antagonists on the glibenclamide-sensitive K+ currents induced by Y-26763 (a K+ channel opener) in follicle-enclosed Xenopus oocytes. (-)-Bepridil and (+)-bepridil similarly suppressed Y-26763-induced K+ currents with IC50 values of 7.8 microM and 7.4 microM, respectively. The Ca2+ channel antagonists, (-)- and (+/-)-verapamil, and inactive (+)-verapamil suppressed Y-26763-induced K+ currents to similar extents and their IC50 values were 63.1 microM and 55.0 microM, respectively. The Ca2+ channel antagonist, SD-3211 and its less potent (-)-isomer, SD-3212, suppressed Y-26763-induced K+ currents with similar IC50 values of 10.7 microM and 8.9 microM, respectively. Of all the Ca2+ channel antagonists tested, only diltiazem exhibited stereoselectivity. The rank order of potencies (IC50 in microM) of four isomers of diltiazem to block Y-26763-induced K+ currents was (+)-trans (4.2) > (-)-trans (13.3) > (-)-cis (35.8) > (+)-cis (75.9), which was, however, opposite to that of their potencies as Ca2+ channel antagonists. These results indicate that blockade by Ca2+ channel antagonists of glibenclamide-sensitive K+ currents in follicle-enclosed Xenopus oocytes is not mediated by Ca2+ channel antagonism.