Comparison of the effluxes of 42K+ and 86Rb+ elicited by cromakalim (BRL 34915) in tonic and phasic vascular tissue

Abstract

The cromakalim-induced effluxes of 42K+ and 86Rb+ were compared in rat aortic segments and in guinea-pig portal vein. In both vessels, low concentrations of cromakalim (0.1 microM) increased the permeability to 86Rb+ 3-4 times less than that to 42K+; at 10 microM the difference was about a factor of 1.3-2. In rat aorta, the threshold concentration of cromakalim for 42K+ efflux was greater than or equal to 0.03 microM; with 86Rb+ as the tracer ion it was 0.1 microM. At similar concentrations, cromakalim relaxed the tension of aortic segments precontracted with 23 mM KCl (IC50 = 0.06 +/- 0.01 microM). However, no concomitant increase in 42K+ or 86Rb+ efflux could be detected from this stimulated preparation at these concentrations. In guinea-pig portal vein, 42K+ efflux measurements were performed in the presence and absence of the dihydropyridine Ca2+ entry blocker PN 200-110 (isradipine) yielding comparable results. In the presence of PN 200-110, where spontaneous activity and the K+ efflux associated with it were abolished, the threshold concentration of cromakalim for 42K+ efflux was 0.02 microM as compared to 0.06 microM for 86Rb+ efflux. In the absence of PN 200-110, spontaneous activity of the portal vein was inhibited by 70% and 90% at these concentrations. In double isotope experiments, the K+ channel inhibitor tetraethylammonium did not discriminate between the effluxes of 42K+ and 86Rb+ stimulated by cromakalim. It is concluded that in the two vascular tissues examined, cromakalim increased the permeability to 42K+ more than to 86Rb+, the difference being more marked at low cromakalim concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)