Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1992 Mar;105(3):549–556. doi: 10.1111/j.1476-5381.1992.tb09017.x

Effects of BRL 38227 on potassium currents in smooth muscle cells isolated from rabbit portal vein and human mesenteric artery.

S N Russell 1, S V Smirnov 1, P I Aaronson 1
PMCID: PMC1908452  PMID: 1628142

Abstract

1. Single smooth muscle cells were isolated from the rabbit portal vein and the human mesenteric artery and whole cell currents recorded at room temperature from either cell type by the whole cell voltage clamp technique. 2. In the rabbit portal vein cells addition of 10 microM BRL 38227 induced a quasi-instantaneous, voltage-insensitive and time-independent current which had a reversal potential of -75 mV under experimental conditions where the calculated EK was -83 mV. 3. Cells were held at 0 mV and BRL 38227 was added cumulatively to construct a dose-response relationship. BRL 38227 (0.03-10 microM) caused a dose-dependent outward shift in the holding current with an EC50 of 1.3 microM. 4. BRL 38227 (10 microM) had no effect on the delayed rectifier K+ current measured in the presence of 5 mM tetraethylammonium and no effect on the Ca(2+)-activated K+ current measured in the presence of 5 mM 4-aminopyridine. Similarly BRL 38227 had no effect on the Ca2+ current. 5. The BRL 38227-induced current was blocked by glibenclamide (10 microM) and phentolamine (100 microM), specific blockers of the ATP-sensitive K+ current in single cells. 6. In human isolated mesenteric artery cells, BRL 38227 (10 microM) induced a glibenclamide-sensitive current similar to, but smaller than, that observed in the rabbit portal vein. 7. We conclude that in these cells, BRL 38227 activates a potassium conductance which has the electrophysiological and pharmacological characteristics of ATP-sensitive K+ channels.

Full text

PDF
549

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ashcroft S. J., Ashcroft F. M. Properties and functions of ATP-sensitive K-channels. Cell Signal. 1990;2(3):197–214. doi: 10.1016/0898-6568(90)90048-f. [DOI] [PubMed] [Google Scholar]
  2. Beech D. J., Bolton T. B. A voltage-dependent outward current with fast kinetics in single smooth muscle cells isolated from rabbit portal vein. J Physiol. 1989 May;412:397–414. doi: 10.1113/jphysiol.1989.sp017623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beech D. J., Bolton T. B. Properties of the cromakalim-induced potassium conductance in smooth muscle cells isolated from the rabbit portal vein. Br J Pharmacol. 1989 Nov;98(3):851–864. doi: 10.1111/j.1476-5381.1989.tb14614.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beech D. J., Bolton T. B. Two components of potassium current activated by depolarization of single smooth muscle cells from the rabbit portal vein. J Physiol. 1989 Nov;418:293–309. doi: 10.1113/jphysiol.1989.sp017841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Belles B., Hescheler J., Trube G. Changes of membrane currents in cardiac cells induced by long whole-cell recordings and tolbutamide. Pflugers Arch. 1987 Aug;409(6):582–588. doi: 10.1007/BF00584657. [DOI] [PubMed] [Google Scholar]
  6. Benham C. D., Bolton T. B. Spontaneous transient outward currents in single visceral and vascular smooth muscle cells of the rabbit. J Physiol. 1986 Dec;381:385–406. doi: 10.1113/jphysiol.1986.sp016333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bolton T. B., Lim S. P. Properties of calcium stores and transient outward currents in single smooth muscle cells of rabbit intestine. J Physiol. 1989 Feb;409:385–401. doi: 10.1113/jphysiol.1989.sp017504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cook D. L., Hales C. N. Intracellular ATP directly blocks K+ channels in pancreatic B-cells. Nature. 1984 Sep 20;311(5983):271–273. doi: 10.1038/311271a0. [DOI] [PubMed] [Google Scholar]
  9. Cook N. S. The pharmacology of potassium channels and their therapeutic potential. Trends Pharmacol Sci. 1988 Jan;9(1):21–28. doi: 10.1016/0165-6147(88)90238-6. [DOI] [PubMed] [Google Scholar]
  10. Gelband C. H., Lodge N. J., Van Breemen C. A Ca2+-activated K+ channel from rabbit aorta: modulation by cromakalim. Eur J Pharmacol. 1989 Aug 22;167(2):201–210. doi: 10.1016/0014-2999(89)90580-3. [DOI] [PubMed] [Google Scholar]
  11. Hamilton T. C., Weston A. H. Cromakalim, nicorandil and pinacidil: novel drugs which open potassium channels in smooth muscle. Gen Pharmacol. 1989;20(1):1–9. doi: 10.1016/0306-3623(89)90052-9. [DOI] [PubMed] [Google Scholar]
  12. Hume J. R., Leblanc N. Macroscopic K+ currents in single smooth muscle cells of the rabbit portal vein. J Physiol. 1989 Jun;413:49–73. doi: 10.1113/jphysiol.1989.sp017641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Inoue I., Nakaya Y., Nakaya S., Mori H. Extracellular Ca2+-activated K channel in coronary artery smooth muscle cells and its role in vasodilation. FEBS Lett. 1989 Sep 25;255(2):281–284. doi: 10.1016/0014-5793(89)81106-8. [DOI] [PubMed] [Google Scholar]
  14. Inoue R., Kitamura K., Kuriyama H. Two Ca-dependent K-channels classified by the application of tetraethylammonium distribute to smooth muscle membranes of the rabbit portal vein. Pflugers Arch. 1985 Oct;405(3):173–179. doi: 10.1007/BF00582557. [DOI] [PubMed] [Google Scholar]
  15. Inoue R., Okabe K., Kitamura K., Kuriyama H. A newly identified Ca2+ dependent K+ channel in the smooth muscle membrane of single cells dispersed from the rabbit portal vein. Pflugers Arch. 1986 Feb;406(2):138–143. doi: 10.1007/BF00586674. [DOI] [PubMed] [Google Scholar]
  16. Kajioka S., Nakashima M., Kitamura K., Kuriyama H. Mechanisms of vasodilatation induced by potassium-channel activators. Clin Sci (Lond) 1991 Aug;81(2):129–139. doi: 10.1042/cs0810129. [DOI] [PubMed] [Google Scholar]
  17. Kajioka S., Oike M., Kitamura K. Nicorandil opens a calcium-dependent potassium channel in smooth muscle cells of the rat portal vein. J Pharmacol Exp Ther. 1990 Sep;254(3):905–913. [PubMed] [Google Scholar]
  18. McPherson G. A., Angus J. A. Phentolamine and structurally related compounds selectively antagonize the vascular actions of the K+ channel opener, cromromakalim. Br J Pharmacol. 1989 Jul;97(3):941–949. doi: 10.1111/j.1476-5381.1989.tb12035.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Murray M. A., Boyle J. P., Small R. C. Cromakalim-induced relaxation of guinea-pig isolated trachealis: antagonism by glibenclamide and by phentolamine. Br J Pharmacol. 1989 Nov;98(3):865–874. doi: 10.1111/j.1476-5381.1989.tb14615.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nielsen-Kudsk J. E., Bang L., Brønsgaard A. M. Glibenclamide blocks the relaxant action of pinacidil and cromakalim in airway smooth muscle. Eur J Pharmacol. 1990 May 16;180(2-3):291–296. doi: 10.1016/0014-2999(90)90312-t. [DOI] [PubMed] [Google Scholar]
  21. Noma A. ATP-regulated K+ channels in cardiac muscle. Nature. 1983 Sep 8;305(5930):147–148. doi: 10.1038/305147a0. [DOI] [PubMed] [Google Scholar]
  22. Okabe K., Kajioka S., Nakao K., Kitamura K., Kuriyama H., Weston A. H. Actions of cromakalim on ionic currents recorded from single smooth muscle cells of the rat portal vein. J Pharmacol Exp Ther. 1990 Feb;252(2):832–839. [PubMed] [Google Scholar]
  23. Plant T. D., Henquin J. C. Phentolamine and yohimbine inhibit ATP-sensitive K+ channels in mouse pancreatic beta-cells. Br J Pharmacol. 1990 Sep;101(1):115–120. doi: 10.1111/j.1476-5381.1990.tb12099.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Post J. M., Stevens R. J., Sanders K. M., Hume J. R. Effect of cromakalim and lemakalim on slow waves and membrane currents in colonic smooth muscle. Am J Physiol. 1991 Feb;260(2 Pt 1):C375–C382. doi: 10.1152/ajpcell.1991.260.2.C375. [DOI] [PubMed] [Google Scholar]
  25. Quast U., Cook N. S. Moving together: K+ channel openers and ATP-sensitive K+ channels. Trends Pharmacol Sci. 1989 Nov;10(11):431–435. doi: 10.1016/S0165-6147(89)80003-3. [DOI] [PubMed] [Google Scholar]
  26. Spruce A. E., Standen N. B., Stanfield P. R. Voltage-dependent ATP-sensitive potassium channels of skeletal muscle membrane. Nature. 1985 Aug 22;316(6030):736–738. doi: 10.1038/316736a0. [DOI] [PubMed] [Google Scholar]
  27. Standen N. B., Quayle J. M., Davies N. W., Brayden J. E., Huang Y., Nelson M. T. Hyperpolarizing vasodilators activate ATP-sensitive K+ channels in arterial smooth muscle. Science. 1989 Jul 14;245(4914):177–180. doi: 10.1126/science.2501869. [DOI] [PubMed] [Google Scholar]
  28. Weir S. W., Weston A. H. The effects of BRL 34915 and nicorandil on electrical and mechanical activity and on 86Rb efflux in rat blood vessels. Br J Pharmacol. 1986 May;88(1):121–128. doi: 10.1111/j.1476-5381.1986.tb09478.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES