Abstract
1. In circular muscle strips of the antrum of guinea-pig stomach, the effects of cromakalim were studied on mechanical activity and intracellular membrane potential. 2. Cromakalim inhibited mechanical activity at concentrations higher than 1 microM, accompanied by membrane hyperpolarization and a decrease in membrane resistance. The hyperpolarization was markedly potentiated in K(+)-free solution and was still observed in the absence of Na+. 3. Slow wave electrical activity was relatively resistant to cromakalim. Changes in its amplitude and frequency were not consistent but blockade of slow waves was never observed. In many preparations cromakalim induced spike-like potentials at the top of slow waves, or when spike-like potentials already existed they were potentiated. However, mechanical activity was always inhibited. 4. Inhibition by cromakalim of the phasic contractions associated with the slow waves, could not be reversed by increasing the external K+ concentration (12-30 mM). 5. The results suggest that in guinea-pig stomach muscle mechanical suppression by cromakalim does not simply result from membrane hyperpolarization or from inhibition of slow waves. A clear dissociation was found between the mechanical and electrical activities. Slow waves, particularly their frequency, are relatively insensitive to membrane hyperpolarization.
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- Abe Y., Tomita T. Cable properties of smooth muscle. J Physiol. 1968 May;196(1):87–100. doi: 10.1113/jphysiol.1968.sp008496. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Allen S. L., Boyle J. P., Cortijo J., Foster R. W., Morgan G. P., Small R. C. Electrical and mechanical effects of BRL34915 in guinea-pig isolated trachealis. Br J Pharmacol. 1986 Oct;89(2):395–405. doi: 10.1111/j.1476-5381.1986.tb10273.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bray K. M., Weston A. H., Duty S., Newgreen D. T., Longmore J., Edwards G., Brown T. J. Differences between the effects of cromakalim and nifedipine on agonist-induced responses in rabbit aorta. Br J Pharmacol. 1991 Feb;102(2):337–344. doi: 10.1111/j.1476-5381.1991.tb12175.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cavero I., Mondot S., Mestre M. Vasorelaxant effects of cromakalim in rats are mediated by glibenclamide-sensitive potassium channels. J Pharmacol Exp Ther. 1989 Mar;248(3):1261–1268. [PubMed] [Google Scholar]
- Chihara S., Tomita T. Mechanical and electrical responses to alpha-adrenoceptor activation in the circular muscle of guinea-pig stomach. Br J Pharmacol. 1987 Aug;91(4):789–798. doi: 10.1111/j.1476-5381.1987.tb11277.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Dinh Xuan A. T., Higenbottam T. W., Clelland C., Pepke-Zaba J., Cremona G., Wallwork J. Impairment of pulmonary endothelium-dependent relaxation in patients with Eisenmenger's syndrome. Br J Pharmacol. 1990 Jan;99(1):9–10. doi: 10.1111/j.1476-5381.1990.tb14643.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Farraway L., Huizinga J. D. Potassium channel activation by cromakalim affects the slow wave type action potential of colonic smooth muscle. J Pharmacol Exp Ther. 1991 Apr;257(1):35–41. [PubMed] [Google Scholar]
- Golenhofen K., Lammel E. Selective suppression of some components of spontaneous activity in various types of smooth muscle by iproveratril (Verapamil). Pflugers Arch. 1972;331(3):233–243. [PubMed] [Google Scholar]
- Hamilton T. C., Weir S. W., Weston A. H. Comparison of the effects of BRL 34915 and verapamil on electrical and mechanical activity in rat portal vein. Br J Pharmacol. 1986 May;88(1):103–111. doi: 10.1111/j.1476-5381.1986.tb09476.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hollingsworth M., Amédée T., Edwards D., Mironneau J., Savineau J. P., Small R. C., Weston A. H. The relaxant action of BRL 34915 in rat uterus. Br J Pharmacol. 1987 Aug;91(4):803–813. doi: 10.1111/j.1476-5381.1987.tb11279.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ito K., Kanno T., Suzuki K., Masuzawa-Ito K., Takewaki T., Ohashi H., Asano M., Suzuki H. Effects of cromakalim on the contraction and the membrane potential of the circular smooth muscle of guinea-pig stomach. Br J Pharmacol. 1992 Feb;105(2):335–340. doi: 10.1111/j.1476-5381.1992.tb14255.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McPherson G. A., Angus J. A. Characterization of responses to cromakalim and pinacidil in smooth and cardiac muscle by use of selective antagonists. Br J Pharmacol. 1990 Jun;100(2):201–206. doi: 10.1111/j.1476-5381.1990.tb15782.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakao K., Okabe K., Kitamura K., Kuriyama H., Weston A. H. Characteristics of cromakalim-induced relaxations in the smooth muscle cells of guinea-pig mesenteric artery and vein. Br J Pharmacol. 1988 Nov;95(3):795–804. doi: 10.1111/j.1476-5381.1988.tb11707.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ohba M., Sakamoto Y., Tomita T. Effects of sodium, potassium and calcium ions on the slow wave in the circular muscle of the guinea-pig stomach. J Physiol. 1977 May;267(1):167–180. doi: 10.1113/jphysiol.1977.sp011806. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Quast U. Potassium channel openers: pharmacological and clinical aspects. Fundam Clin Pharmacol. 1992;6(7):279–293. doi: 10.1111/j.1472-8206.1992.tb00122.x. [DOI] [PubMed] [Google Scholar]
- Syed M. M., Parekh A. B., Tomita T. Receptors involved in mechanical responses to catecholamines in the circular muscle of guinea-pig stomach treated with meclofenamate. Br J Pharmacol. 1990 Dec;101(4):809–814. doi: 10.1111/j.1476-5381.1990.tb14162.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Szurszewski J. H. A study of the canine gastric action potential in the presence of tetraethylammonium chloride. J Physiol. 1978 Apr;277:91–102. doi: 10.1113/jphysiol.1978.sp012262. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weir S. W., Weston A. H. Effect of apamin on responses to BRL 34915, nicorandil and other relaxants in the guinea-pig taenia caeci. Br J Pharmacol. 1986 May;88(1):113–120. doi: 10.1111/j.1476-5381.1986.tb09477.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weston A. H., Edwards G. Recent progress in potassium channel opener pharmacology. Biochem Pharmacol. 1992 Jan 9;43(1):47–54. doi: 10.1016/0006-2952(92)90659-7. [DOI] [PubMed] [Google Scholar]
- Weston A. H. Smooth muscle K+ channel openers; their pharmacology and clinical potential. Pflugers Arch. 1989;414 (Suppl 1):S99–105. doi: 10.1007/BF00582256. [DOI] [PubMed] [Google Scholar]
- 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]
