Abstract
The rank order of potency of a series of benzopyran and cyanoguanidine K+ channel openers (KCOs) for causing relaxation of the PGF2α-precontracted porcine coronary artery was determined. Glyburide, an inhibitor of KATP channels, showed an apparent competitive inhibition of the vasorelaxant activity of the KCOs. The pA2 values of glyburide when cromakalim and CGP 14877 (P1060) were used as vasorelaxants were 7.66 and 7.83, respectively. Charybdotoxin (40 nM), an inhibitor of BKCa channels, also caused a significant inhibition of the cromakalim mediated relaxation of the porcine coronary artery. In order to clarify the site of action of these KCOs, we identified a K+ channel current in single porcine coronary arterial cells and measured channel activity in the presence of these compounds. The prominent K+ ion current in these cells had characteristics typical of the conventional large Ca2+-activated K+ channel BKCa present in other smooth muscle cells. Using symmetrical K+ concentrations, the channel had a conductance of 214 pS and was found to be sensitive to [Ca2+]i and membrane potential. The KCOs were found to reversibly increase the open probability (Po) of the channel without changing channel conductance. The potency of the KCOs to increase K+ channel opening was similar to the potency of these compounds to cause coronary artery relaxation. These results indicate that the porcine coronary artery contains the BKCa channel and that this channel, along with other types of K+ channels (KATP), mediate the vasorelaxant effects of K+ channel openers.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Arunlakshana O, Schild HO (1959) Some quantitative uses of drug antagonists. Br J Pharmacol Chemother 14:48–58
Ashcroft FM (1988) Adenosine 5′-triphosphate-sensitive potassium channels. Ann Rev Neurosci 11:97–118
Beech DJ, Zhang H, Nakao K, Bolton TB (1993) Single channel and whole-cell K-currents evoked by leveromakalim in smooth muscle cells from the rabbit portal vein. Br J Pharmacol 110:583–590
Bonev AD, Nelson MT (1993) ATP-sensitive potassium channels in smooth muscle cells from guinea pig urinary bladder. Am J Physiol 264:C1190-C1200
BoSmith RE, Briggs I, Grant TL, Grimwood S, Russell NJW, Stone MA, Wickenden AD (1989) A comparison of the effects and interactions of cromakalim and glibenclamide in cardiac and vascular tissues. Pflügers Arch 414:S190
Cavero I, Mondot S, Mestre M (1989) Vasorelaxant effects of cromakalim in rats are mediated by glibenclamide-sensitive potassium channels. J Pharmacol Exp Ther 248:1261–1268
Dart C, Standen NB (1993) Adenosine-activated potassium current in smooth muscle cells isolated from the pig coronary artery. J Physiol 471:76–786
DeLean A, Munson PJ, Rodbard D (1978) Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose-response curves. Am J Physiol 235:E97–102
Eckman DM, Frankovich JD, Keef KD (1992) Comparisons of the action of acetylcholine and BRL 38227 in the guinea-pig coronary artery. Br J Pharmacol 106:9–16
Fletcher JE, Shrager RI (1973) A user's guide to least squares model fitting. Tech Rep 1 Bethesda Md., USA Natl Inst Health
Gelband CH, McCullough JR (1993) Modulation of rabbit aortic Ca2+-activated K+ channels by pinacidil, cromakalim, and glibenclamide. Am J Physiol 264:C1119-C1127
Gelband CH, Lodge NJ, Van Breemen C (1989) A Ca2+-activated K+ channel from rabbit aorta: modulation by cromakalim. Eur J Pharmacol 167:201–210
Gopalakrishan M, Janis RA, Triggle DJ (1993) ATP-sensitive K+ channels: Pharmacologic properties, regulation and therapeutic potential. Drug Dev Res 28:95–127
Hamil OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch 391:85–100
Hamilton TC, Weir SW, Weston AH (1986) Comparison of the effects of BRL 34915 and verapamil on electrical and mechanical activity in rat portal vein. Br J Pharmacol 88:103–111
Hu S, Kim HS, Okolie P, Weiss GB (1990) Alterations by glyburide of effects of BRL 34915 and P 1060 on contraction, 86Rb efflux and the maxi-K+ channel in rat portal vein. J Pharmacol Exp Ther 253:771–777
Imai S, Takeda K (1967) Calcium and contraction of heart and smooth muscle. Nature 313:1044–1045
Isenberg G, Klockner U (1982) Calcium tolerant ventricular myocytes prepared by preincubation in a “KB” medium. Pflügers Arch 395:6–18
Kajioka S, Oike M, Kitamura K (1990) Nicorandil opens a calcium-dependent potassium channel in smooth muscle cells of the rat portal vein. J Pharmacol Exp Ther 254:905–913
Kamouchi M, Kajioka S, Sakai T, Kitamura K, Kuriyama H (1993) A target K+ channel for the LP-805-induced hyperpolarization in smooth muscle cells of the rabbit portal vein. NaunynSchmiedeberg's Arch Pharmacol 347:329–335
Klockner U, Isenberg G (1991) ATP suppresses activity of Ca2+-activated K+ channels by Ca2+ chelation. Pflügers Arch 420:101–105
Klockner U, Trieschmann U, Isenberg G (1989) Pharmacological modulation of calcium and potassium channels in isolated vascular smooth muscle cells. Drug Res 39:120–126
Latorre R, Oberhauser A, Labarca P, Alvarez O (1989) Varieties of calcium-activated potassium channels. Ann Rev Physiol 51: p385–399
Laurent F, Michel A, Bonnet PA, Chapat JP, Boucard M (1993) Evaluation of the relaxant effects of SCA40, a novel charybdotoxin-sensitive potassium channel opener, in guinea-pig isolated trachealis. Br J Pharmacol 108:622–626
Noack T, Edwards G, Deitmer P, Weston AH (1992) Potassium channel modulation in rat portal vein by ATP depletion: a comparison with the effects of levcromakalim (BRL 38227). Br J Pharmacol 107:945–955
Quast U, Cook N (1989) In vitro and in vivo comparison of two K+ channel openers, diazoxide and cromakalim, and their inhibition by cromakalim. J Pharmacol Exp Ther 250:261–271
Rodbard D, Frazier GR (1975) Statistical analysis of radioligand assay data. Methods Enzymel 37:3–22
Standen NB, Quayle JM, Davies NW, Brayden JE, Huang Y, Nelson MT (1989) Hyperpolarizing vasodilators activate ATP-sensitive K+ channels in arterial smooth muscle. Science 245:177–180
Steinberg MI, Ertel P, Smallwood JK, Wyss V, Zimmerman K (1988) The relation between vascular relaxant and cardiac electrophysiological effects of pinacidil. J Cardiovasc Pharmacol 12:S30-S40
Suarez-Kurtz G, Garcia ML, Kaczorowski GJ (1991) Effects of charybdotoxin and iberiotoxin on the spontaneous motility and tonus of different guinea pig smooth muscle tissues. J Pharmacol Exp Ther 259:439–443
Weston AH, Edwards G (1992) Recent progress in potassium channel opener pharmacology. Biochem Pharmacol 43:47–54
Weston AH, Southerton JS, Bray KM, Newgreen DT, Taylor SG (1988) The mode of action of pinacidil and its analogs P 1060 and P 1368: results of studies in rat blood vessels. J Cardiovasc Pharmacol 12: S10-S16
Winquist RJ, Heaney LA, Wallace AA, Baskin EP, Stein RB, Garcia ML, Kaczorowski GJ (1989) Glyburide blocks the relaxation response to BRL 34915 (cromakalim), minoxidil sulfate and diazoxide in vascular smooth muscle. J Pharmacol Exp Ther 248:149–156
Xu X, Lee KS (1994) Characterization of the ATP-inhibited K+ current in canine coronary smooth muscle cells. Pflügers Arch 427:110–120
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Balwierczak, J.L., Krulan, C.M., Kim, H.S. et al. Evidence that BKCa channel activation contributes to K+ channel opener induced relaxation of the porcine coronary artery. Naunyn-Schmiedeberg's Arch Pharmacol 352, 213–221 (1995). https://doi.org/10.1007/BF00176777
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00176777