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. 1998 Oct;75(4):1793–1800. doi: 10.1016/S0006-3495(98)77621-0

Basal activation of ATP-sensitive potassium channels in murine colonic smooth muscle cell.

S D Koh 1, K K Bradley 1, M G Rae 1, K D Keef 1, B Horowitz 1, K M Sanders 1
PMCID: PMC1299851  PMID: 9746521

Abstract

The function and molecular expression of ATP-sensitive potassium (KATP) channels in murine colonic smooth muscle was investigated by intracellular electrical recording from intact muscles, patch-clamp techniques on isolated smooth muscle myocytes, and reverse transcription polymerase chain reaction (RT-PCR) on isolated cells. Lemakalim (1 microM) caused hyperpolarization of intact muscles (17. 2 +/- 3 mV). The hyperpolarization was blocked by glibenclamide (1-10 microM). Addition of glibenclamide (10 microM) alone resulted in membrane depolarization (9.3 +/- 1.7 mV). Lemakalim induced an outward current of 15 +/- 3 pA in isolated myocytes bathed in 5 mM external K+ solution. Application of lemakalim to cells in symmetrical K+ solutions (140/140 mM) resulted in a 97 +/- 5 pA inward current. Both currents were blocked by glibenclamide (1 microM). Pinacidil (1 microM) also activated an inwardly rectifying current that was insensitive to 4-aminopyridine and barium. In single-channel studies, lemakalim (1 microM) and diazoxide (300 microM) increased the open probability of a 27-pS K+ channel. Openings of these channels decreased with time after patch excision. Application of ADP (1 mM) or ATP (0.1 mM) to the inner surface of the patches reactivated channel openings. The conductance and characteristics of the channels activated by lemakalim were consistent with the properties of KATP. RT-PCR demonstrated the presence of Kir 6.2 and SUR2B transcripts in colonic smooth muscle cells; transcripts for Kir 6.1, SUR1, and SUR2A were not detected. These molecular studies are the first to identify the molecular components of KATP in colonic smooth muscle cells. Together with the electrophysiological experiments, we conclude that KATP channels are expressed in murine colonic smooth muscle cells and suggest that these channels may be involved in dual regulation of resting membrane potential, excitability, and contractility.

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Selected References

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  1. Ammälä C., Moorhouse A., Ashcroft F. M. The sulphonylurea receptor confers diazoxide sensitivity on the inwardly rectifying K+ channel Kir6.1 expressed in human embryonic kidney cells. J Physiol. 1996 Aug 1;494(Pt 3):709–714. doi: 10.1113/jphysiol.1996.sp021526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ashcroft F. M., Kakei M. ATP-sensitive K+ channels in rat pancreatic beta-cells: modulation by ATP and Mg2+ ions. J Physiol. 1989 Sep;416:349–367. doi: 10.1113/jphysiol.1989.sp017765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Bonev A. D., Nelson M. T. ATP-sensitive potassium channels in smooth muscle cells from guinea pig urinary bladder. Am J Physiol. 1993 May;264(5 Pt 1):C1190–C1200. doi: 10.1152/ajpcell.1993.264.5.C1190. [DOI] [PubMed] [Google Scholar]
  5. Bray K., Quast U. Differential inhibition by tedisamil (KC 8857) and glibenclamide of the responses to cromakalim and minoxidil sulphate in rat isolated aorta. Naunyn Schmiedebergs Arch Pharmacol. 1992 Feb;345(2):244–250. doi: 10.1007/BF00165744. [DOI] [PubMed] [Google Scholar]
  6. Edwards G., Weston A. H. The pharmacology of ATP-sensitive potassium channels. Annu Rev Pharmacol Toxicol. 1993;33:597–637. doi: 10.1146/annurev.pa.33.040193.003121. [DOI] [PubMed] [Google Scholar]
  7. Huizinga J. D., Stern H. S., Chow E., Diamant N. E., El-Sharkawy T. Y. Electrophysiologic control of motility in the human colon. Gastroenterology. 1985 Feb;88(2):500–511. doi: 10.1016/0016-5085(85)90513-x. [DOI] [PubMed] [Google Scholar]
  8. Inagaki N., Gonoi T., Clement J. P., 4th, Namba N., Inazawa J., Gonzalez G., Aguilar-Bryan L., Seino S., Bryan J. Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science. 1995 Nov 17;270(5239):1166–1170. doi: 10.1126/science.270.5239.1166. [DOI] [PubMed] [Google Scholar]
  9. Inagaki N., Tsuura Y., Namba N., Masuda K., Gonoi T., Horie M., Seino Y., Mizuta M., Seino S. Cloning and functional characterization of a novel ATP-sensitive potassium channel ubiquitously expressed in rat tissues, including pancreatic islets, pituitary, skeletal muscle, and heart. J Biol Chem. 1995 Mar 17;270(11):5691–5694. doi: 10.1074/jbc.270.11.5691. [DOI] [PubMed] [Google Scholar]
  10. Isomoto S., Kondo C., Yamada M., Matsumoto S., Higashiguchi O., Horio Y., Matsuzawa Y., Kurachi Y. A novel sulfonylurea receptor forms with BIR (Kir6.2) a smooth muscle type ATP-sensitive K+ channel. J Biol Chem. 1996 Oct 4;271(40):24321–24324. doi: 10.1074/jbc.271.40.24321. [DOI] [PubMed] [Google Scholar]
  11. Itoh T., Seki N., Suzuki S., Ito S., Kajikuri J., Kuriyama H. Membrane hyperpolarization inhibits agonist-induced synthesis of inositol 1,4,5-trisphosphate in rabbit mesenteric artery. J Physiol. 1992;451:307–328. doi: 10.1113/jphysiol.1992.sp019166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kajioka S., Kitamura K., Kuriyama H. Guanosine diphosphate activates an adenosine 5'-triphosphate-sensitive K+ channel in the rabbit portal vein. J Physiol. 1991 Dec;444:397–418. doi: 10.1113/jphysiol.1991.sp018885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kamei K., Yoshida S., Imagawa J., Nabata H., Kuriyama H. Regional and species differences in glyburide-sensitive K+ channels in airway smooth muscles as estimated from actions of KC 128 and levcromakalim. Br J Pharmacol. 1994 Nov;113(3):889–897. doi: 10.1111/j.1476-5381.1994.tb17076.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kamouchi M., Kitamura K. Regulation of ATP-sensitive K+ channels by ATP and nucleotide diphosphate in rabbit portal vein. Am J Physiol. 1994 May;266(5 Pt 2):H1687–H1698. doi: 10.1152/ajpheart.1994.266.5.H1687. [DOI] [PubMed] [Google Scholar]
  15. Koh S. D., Dick G. M., Sanders K. M. Small-conductance Ca(2+)-dependent K+ channels activated by ATP in murine colonic smooth muscle. Am J Physiol. 1997 Dec;273(6 Pt 1):C2010–C2021. doi: 10.1152/ajpcell.1997.273.6.C2010. [DOI] [PubMed] [Google Scholar]
  16. Kovacs R. J., Nelson M. T. ATP-sensitive K+ channels from aortic smooth muscle incorporated into planar lipid bilayers. Am J Physiol. 1991 Aug;261(2 Pt 2):H604–H609. doi: 10.1152/ajpheart.1991.261.2.H604. [DOI] [PubMed] [Google Scholar]
  17. Kubo M., Quayle J. M., Standen N. B. Angiotensin II inhibition of ATP-sensitive K+ currents in rat arterial smooth muscle cells through protein kinase C. J Physiol. 1997 Sep 15;503(Pt 3):489–496. doi: 10.1111/j.1469-7793.1997.489bg.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Miyoshi Y., Nakaya Y. Angiotensin II blocks ATP-sensitive K+ channels in porcine coronary artery smooth muscle cells. Biochem Biophys Res Commun. 1991 Dec 16;181(2):700–706. doi: 10.1016/0006-291x(91)91247-a. [DOI] [PubMed] [Google Scholar]
  19. Miyoshi Y., Nakaya Y., Wakatsuki T., Nakaya S., Fujino K., Saito K., Inoue I. Endothelin blocks ATP-sensitive K+ channels and depolarizes smooth muscle cells of porcine coronary artery. Circ Res. 1992 Mar;70(3):612–616. doi: 10.1161/01.res.70.3.612. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Nakashima M., Vanhoutte P. M. Isoproterenol causes hyperpolarization through opening of ATP-sensitive potassium channels in vascular smooth muscle of the canine saphenous vein. J Pharmacol Exp Ther. 1995 Jan;272(1):379–384. [PubMed] [Google Scholar]
  22. Nelson M. T., Huang Y., Brayden J. E., Hescheler J., Standen N. B. Arterial dilations in response to calcitonin gene-related peptide involve activation of K+ channels. Nature. 1990 Apr 19;344(6268):770–773. doi: 10.1038/344770a0. [DOI] [PubMed] [Google Scholar]
  23. Nelson M. T., Quayle J. M. Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol. 1995 Apr;268(4 Pt 1):C799–C822. doi: 10.1152/ajpcell.1995.268.4.C799. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Quast U., Cook N. S. In vitro and in vivo comparison of two K+ channel openers, diazoxide and cromakalim, and their inhibition by glibenclamide. J Pharmacol Exp Ther. 1989 Jul;250(1):261–271. [PubMed] [Google Scholar]
  26. Quayle J. M., Bonev A. D., Brayden J. E., Nelson M. T. Calcitonin gene-related peptide activated ATP-sensitive K+ currents in rabbit arterial smooth muscle via protein kinase A. J Physiol. 1994 Feb 15;475(1):9–13. doi: 10.1113/jphysiol.1994.sp020045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Quayle J. M., Bonev A. D., Brayden J. E., Nelson M. T. Pharmacology of ATP-sensitive K+ currents in smooth muscle cells from rabbit mesenteric artery. Am J Physiol. 1995 Nov;269(5 Pt 1):C1112–C1118. doi: 10.1152/ajpcell.1995.269.5.C1112. [DOI] [PubMed] [Google Scholar]
  28. Quayle J. M., Standen N. B., Stanfield P. R. The voltage-dependent block of ATP-sensitive potassium channels of frog skeletal muscle by caesium and barium ions. J Physiol. 1988 Nov;405:677–697. doi: 10.1113/jphysiol.1988.sp017355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sakura H., Ammälä C., Smith P. A., Gribble F. M., Ashcroft F. M. Cloning and functional expression of the cDNA encoding a novel ATP-sensitive potassium channel subunit expressed in pancreatic beta-cells, brain, heart and skeletal muscle. FEBS Lett. 1995 Dec 27;377(3):338–344. doi: 10.1016/0014-5793(95)01369-5. [DOI] [PubMed] [Google Scholar]
  30. Shyng S., Nichols C. G. Octameric stoichiometry of the KATP channel complex. J Gen Physiol. 1997 Dec;110(6):655–664. doi: 10.1085/jgp.110.6.655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Smith T. K., Reed J. B., Sanders K. M. Origin and propagation of electrical slow waves in circular muscle of canine proximal colon. Am J Physiol. 1987 Feb;252(2 Pt 1):C215–C224. doi: 10.1152/ajpcell.1987.252.2.C215. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Teramoto N., Brading A. F. Activation by levcromakalim and metabolic inhibition of glibenclamide-sensitive K channels in smooth muscle cells of pig proximal urethra. Br J Pharmacol. 1996 Jun;118(3):635–642. doi: 10.1111/j.1476-5381.1996.tb15448.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Teramoto N., Brading A. F. Nicorandil activates glibenclamide-sensitive K+ channels in smooth muscle cells of pig proximal urethra. J Pharmacol Exp Ther. 1997 Jan;280(1):483–491. [PubMed] [Google Scholar]
  35. Yokoshiki H., Sunagawa M., Seki T., Sperelakis N. ATP-sensitive K+ channels in pancreatic, cardiac, and vascular smooth muscle cells. Am J Physiol. 1998 Jan;274(1 Pt 1):C25–C37. doi: 10.1152/ajpcell.1998.274.1.C25. [DOI] [PubMed] [Google Scholar]
  36. Zhang H. L., Bolton T. B. Two types of ATP-sensitive potassium channels in rat portal vein smooth muscle cells. Br J Pharmacol. 1996 May;118(1):105–114. doi: 10.1111/j.1476-5381.1996.tb15372.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Zhang L., Bonev A. D., Nelson M. T., Mawe G. M. Activation of ATP-sensitive potassium currents in guinea-pig gall-bladder smooth muscle by the neuropeptide CGRP. J Physiol. 1994 Aug 1;478(Pt 3):483–491. doi: 10.1113/jphysiol.1994.sp020267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. den Hertog A., Van den Akker J., Nelemans A. Effect of cromakalim on smooth muscle cells of guinea-pig taenia caeci. Eur J Pharmacol. 1989 Dec 19;174(2-3):287–291. doi: 10.1016/0014-2999(89)90323-3. [DOI] [PubMed] [Google Scholar]

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