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. 1993 Apr;108(4):991–998. doi: 10.1111/j.1476-5381.1993.tb13496.x

Effects of P1060 and aprikalim on whole-cell currents in rat portal vein; inhibition by glibenclamide and phentolamine.

T Ibbotson 1, G Edwards 1, T Noack 1, A H Weston 1
PMCID: PMC1908130  PMID: 8485637

Abstract

1 Smooth muscle cells of the rat portal vein were dispersed by enzymatic treatment and recordings of whole-cell currents were made by the voltage-clamp technique. The effects of the potassium (K) channel openers, P1060 (0.3-10 microM) and aprikalim (3-30 microM) on these currents were investigated. Antagonism of these agents by glibenclamide and phentolamine was also studied. 2 When cells were clamped at -10 mV, P1060 (1 microM) and aprikalim (3 microM) each induced a slowly-developing K-current (IKCO), the noise of which gradually increased. The rate of onset of IKCO was greater for P1060 than for aprikalim. Current-voltage plots showed that P1060 and aprikalim each caused an approximately 25 mV negative shift of the reversal potential at zero current. 3 P1060 (1 microM) and aprikalim (3 microM) each inhibited the slowly activating, slowly inactivating delayed rectifier current, ITO. 4 Addition of MgATP (5 mM) to the recording pipette inhibited the generation of IKCO by P1060 (1 microM) and reduced the accompanying inhibition of ITO. 5 Stationary fluctuation analysis of the current noise associated with IKCO induced by P1060 (1 microM) or aprikalim (3 microM) at a holding potential of -10 mV indicated that the unitary conductance of the underlying K-channels was 10.5 pS at 0 mV under the quasi-physiological conditions of the experiment. 6 In the absence of K-channel openers, neither phentolamine (30-100 microM) nor glibenclamide (1 microM) affected the magnitude of control non-inactivating currents. However, phentolamine (30-100 microM), but not glibenclamide (1 microM) inhibited the control delayed rectifier current ITO.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Ashcroft F. M. Adenosine 5'-triphosphate-sensitive potassium channels. Annu Rev Neurosci. 1988;11:97–118. doi: 10.1146/annurev.ne.11.030188.000525. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Caro J. F. Effects of glyburide on carbohydrate metabolism and insulin action in the liver. Am J Med. 1990 Aug 20;89(2A):17S–53S. doi: 10.1016/0002-9343(90)90332-8. [DOI] [PubMed] [Google Scholar]
  4. Chan S. L., Dunne M. J., Stillings M. R., Morgan N. G. The alpha 2-adrenoceptor antagonist efaroxan modulates K+ATP channels in insulin-secreting cells. Eur J Pharmacol. 1991 Oct 29;204(1):41–48. doi: 10.1016/0014-2999(91)90833-c. [DOI] [PubMed] [Google Scholar]
  5. Dunne M. J. Block of ATP-regulated potassium channels by phentolamine and other alpha-adrenoceptor antagonists. Br J Pharmacol. 1991 Aug;103(4):1847–1850. doi: 10.1111/j.1476-5381.1991.tb12340.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dunne M. J. Effects of pinacidil, RP 49356 and nicorandil on ATP-sensitive potassium channels in insulin-secreting cells. Br J Pharmacol. 1990 Mar;99(3):487–492. doi: 10.1111/j.1476-5381.1990.tb12955.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Edwards G., Weston A. H. Structure-activity relationships of K+ channel openers. Trends Pharmacol Sci. 1990 Oct;11(10):417–422. doi: 10.1016/0165-6147(90)90149-3. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Faivre J. F., Findlay I. Effects of tolbutamide, glibenclamide and diazoxide upon action potentials recorded from rat ventricular muscle. Biochim Biophys Acta. 1989 Aug 21;984(1):1–5. doi: 10.1016/0005-2736(89)90334-9. [DOI] [PubMed] [Google Scholar]
  10. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  11. Hu S. L., Kim H. S., Okolie P., Weiss G. B. 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. 1990 May;253(2):771–777. [PubMed] [Google Scholar]
  12. Jonas J. C., Plant T. D., Henquin J. C. Imidazoline antagonists of alpha 2-adrenoceptors increase insulin release in vitro by inhibiting ATP-sensitive K+ channels in pancreatic beta-cells. Br J Pharmacol. 1992 Sep;107(1):8–14. doi: 10.1111/j.1476-5381.1992.tb14456.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Klöckner U., Isenberg G. Action potentials and net membrane currents of isolated smooth muscle cells (urinary bladder of the guinea-pig). Pflugers Arch. 1985 Dec;405(4):329–339. doi: 10.1007/BF00595685. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. Noack T., Deitmer P., Edwards G., Weston A. H. Characterization of potassium currents modulated by BRL 38227 in rat portal vein. Br J Pharmacol. 1992 Jul;106(3):717–726. doi: 10.1111/j.1476-5381.1992.tb14400.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Noack T., Edwards G., Deitmer P., Greengrass P., Morita T., Andersson P. O., Criddle D., Wyllie M. G., Weston A. H. The involvement of potassium channels in the action of ciclazindol in rat portal vein. Br J Pharmacol. 1992 May;106(1):17–24. doi: 10.1111/j.1476-5381.1992.tb14286.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Noack T., Edwards G., Deitmer P., Weston A. H. Potassium channel modulation in rat portal vein by ATP depletion: a comparison with the effects of levcromakalim (BRL 38227). Br J Pharmacol. 1992 Dec;107(4):945–955. doi: 10.1111/j.1476-5381.1992.tb13390.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Perozo E., Bezanilla F. Phosphorylation affects voltage gating of the delayed rectifier K+ channel by electrostatic interactions. Neuron. 1990 Nov;5(5):685–690. doi: 10.1016/0896-6273(90)90222-2. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Satake N., Shibata S., Ueda S. Phentolamine-induced rhythmic contractions in bladder detrusor muscle of guinea-pig. Br J Pharmacol. 1984 Dec;83(4):965–971. doi: 10.1111/j.1476-5381.1984.tb16538.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schwietert R., Wilhelm D., Wilffert B., Van Zwieten P. A. The effect of some alpha-adrenoceptor antagonists on spontaneous myogenic activity in the rat portal vein and the putative involvement of ATP-sensitive K+ channels. Eur J Pharmacol. 1992 Jan 28;211(1):87–95. doi: 10.1016/0014-2999(92)90267-8. [DOI] [PubMed] [Google Scholar]
  23. Sheppard D. N., Welsh M. J. Effect of ATP-sensitive K+ channel regulators on cystic fibrosis transmembrane conductance regulator chloride currents. J Gen Physiol. 1992 Oct;100(4):573–591. doi: 10.1085/jgp.100.4.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Silberberg S. D., van Breemen C. An ATP, calcium and voltage sensitive potassium channel in porcine coronary artery smooth muscle cells. Biochem Biophys Res Commun. 1990 Oct 30;172(2):517–522. doi: 10.1016/0006-291x(90)90703-p. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Thuringer D., Escande D. Apparent competition between ATP and the potassium channel opener RP 49356 on ATP-sensitive K+ channels of cardiac myocytes. Mol Pharmacol. 1989 Dec;36(6):897–902. [PubMed] [Google Scholar]
  27. Wettwer E., Scholtysik G., Schaad A., Himmel H., Ravens U. Effects of the new class III antiarrhythmic drug E-4031 on myocardial contractility and electrophysiological parameters. J Cardiovasc Pharmacol. 1991 Mar;17(3):480–487. doi: 10.1097/00005344-199103000-00018. [DOI] [PubMed] [Google Scholar]

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