Potassium Channel Activation in Vascular Smooth Muscle

  • G. Siegel
  • J. Emden
  • K. Wenzel
  • J. Mironneau
  • G. Stock
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 311)


K+ channel opening causing membrane hyperpolarization in vascular smooth muscle and thereby vasodilatation, cannot be rated as the ‘newly discovered’ action principle of certain pharmacological substances but as an ubiquitous physiological mechanism for the relaxation in smooth muscle. Acidification of the serum-pH-value is such an effector influence initiating vasodilatation. Drugs such as pinacidil, nicorandil, minoxidil sulphate and cromakalim effect vasodilatation by membrane hyperpolarization of the vascular smooth muscle cells as well, which in some tissues raises the membrane potential to a value close to the K+ equilibrium potential [36]. Although the number of K+ channels observed is steadily but rapidly increasing, they can still be classified. They are usually subdivided according to their mode of activation. Some are activated strictly voltage-dependently, others by a variation in the intracellular Ca2+ concentration, and some by the internal concentration of ATP, Na+, cyclic nucleotides etc. The heterogeneous group of K+ channel openers may be a potential therapy for hypertension, asthma, peripheral vascular disease, and diseases of the heart and nervous system. The central starting point of their physiological mode of action is the hyperpolarization of the smooth muscle cells which leads to relaxation by closing T- and/or L-type Ca2+ channels without, in the classical sense, the participation of cAMP or cGMP [34]. We would like to discuss this problem from a physiological point of view and venture a wider definition of the term ’K+ channel opener’. This seems to be justified by the fact that cyclic nucleotides also elicit a membrane hyperpolarization in the vascular smooth muscle.


Membrane Potential Vascular Smooth Muscle Cell Outward Current Krebs Solution Human Coronary Artery 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Aprigliano, O., and Hermsmeyer, K., 1976, In vitro denervation of the portal vein and caudal artery of the rat, J. Pharmacol Exp. Ther. 198:568–577.PubMedGoogle Scholar
  2. 2.
    Bolton, T. B., 1979, Mechanisms of action of transmitters and other substances on smooth muscle, Physiol Rev. 59:606–718.PubMedGoogle Scholar
  3. 3.
    Braquet, P., Guinot, P., and Tarrade, T., 1988, Cicletanine: biology, pharmacology and clinical sciences, Drugs Exp. Clin. Res. 14:71–230.Google Scholar
  4. 4.
    Calder, J. A., Schachter, M., and Sever, P. S., 1991, Acute relaxant effect of cicletanine in human subcutaneous resistance arteries, Blood Vessels 28:279.Google Scholar
  5. 5.
    Fidone, S., and González, C., 1982, Catecholamine synthesis in rabbit carotid body in vitro, J. Physiol. (Lond.) 333:69–79.Google Scholar
  6. 6.
    Fidone, S., González, C., and Yoshizaki, K., 1982, Effects of hypoxia on catecholamine synthesis in rabbit carotid body in vitro, J. Physiol. (Lond.) 333:81–91.Google Scholar
  7. 7.
    Fredj, G., 1988, Clinical pharmacokinetics of cicletanine hydrochloride, Drugs Exp. Clin. Res. 14:181–188.PubMedGoogle Scholar
  8. 8.
    Ganitkevich, V.Ya., and Isenberg, G., 1990, Contribution of two types of calcium channels to membrane conductance of single myocytes from guinea-pig coronary artery, J. Physiol. (Lond.) 426:19–42.Google Scholar
  9. 9.
    Grote, J., Siegel, G., Zimmer, K., and Adler, A., 1988, The influence of oxygen tension on membrane potential and tone of canine carotid artery smooth muscle, Adv. Exp. Med. Biol. 222:481–487.PubMedCrossRefGoogle Scholar
  10. 10.
    Haeusler, G., de Peyer, J.-E., and Schultz, G., 1987, Vascular effects of α1- and α2-adrenoceptor agonists in vitro and in hypertensive rats, J. Cardiovasc. Pharmacol. 10 [Suppl. 4]: 15–18.Google Scholar
  11. 11.
    Hashimoto, T., Hirata, M., Itoh, T., Kanmura, Y., and Kuriyama, H., 1986, Inositol 1,4,5-trisphosphate activates pharmacomechanical coupling in smooth muscle of the rabbit mesenteric artery, J. Physiol. (Lond.) 370:605–618.Google Scholar
  12. 12.
    Hennsmeyer, K., 1979, High shortening velocity of isolated single arterial muscle cells, Experientia 35:1599–1602.CrossRefGoogle Scholar
  13. 13.
    Kajiwara, M., Droogmans, G., and Casteels, R., 1984, Effects of 2-nicotinamidoethylnitrate (nicorandil) on excitation-contraction coupling in the smooth muscle cells of rabbit ear artery, J. Pharmacol. Exp. Ther. 230:462–468.PubMedGoogle Scholar
  14. 14.
    Kauser, K., Clark, J. E., Masters, B. S., Ortiz de Montellano, P. R., Ma, Y.-H., Harder, D. R., and Roman, R. J., 1991, Inhibitors of cytochrome P-450 attenuate the myogenic response of dog renal arcuate arteries, Circ. Res. 68:1154-1163.PubMedCrossRefGoogle Scholar
  15. 15.
    Loirand, G., Pacaud, P., Mironneau, C., and Mironneau, J., 1986, Evidence for two distinct calcium channels in rat vascular smooth muscle cells in short-term primary culture, Pflügers Arch. 407:566–568.PubMedCrossRefGoogle Scholar
  16. 16.
    Nelson, M. T., Patlak, J. B., Worley, J. F., and Standen, N. B., 1990, Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone, Am. J. Physiol. 259:C3–C18.PubMedGoogle Scholar
  17. 17.
    Northover, B. J., 1980, The membrane potential of vascular endothelial cells, Adv. Microcirc. 9:135–160.Google Scholar
  18. 18.
    Rüegg, J. C, 1986, “Calcium in muscle activation”, Springer-Verlag, Berlin Heidelberg New York London Paris Tokyo.CrossRefGoogle Scholar
  19. 19.
    Sadoshima, J.-I., Akaike, N., Kanaide, H., and Nakamura, M., 1988, Cyclic AMP modulates Ca-activated K channel in cultured smooth muscle cells of rat aortas, Am. J. Physiol. 255: H754–H759.PubMedGoogle Scholar
  20. 20.
    Shaw, K., Montagne, W., and Pallot, D. J., 1990, Biochemical studies on the release of catecholamines from the rat carotid body in vitro, in: “Arterial Chemoreception”, C. Eyzaguirre, S. J. Fidone, R. S. Fitzgerald, S. Lahiri, D. M. McDonald, eds., Springer-Verlag, New York Berlin Heidelberg London Paris Tokyo Hong Kong, pp 87–91.CrossRefGoogle Scholar
  21. 21.
    Siegel, G., 1986, Membranphysiologische Grundlagen der peripheren Gefäßregulation, Physiol., akt. 1:31–52.Google Scholar
  22. 22.
    Siegel, G., 1991, Garlic and vasoregulation, Cardiology in Practice [Suppl.], p 7.Google Scholar
  23. 23.
    Siegel, G., Carl, A., Adler, A., and Stock, G., 1989, Effect of the prostacyclin analogue iloprost on K+ permeability in the smooth muscle cells of the canine carotid artery, Eicosanoids 2:213–222.PubMedGoogle Scholar
  24. 24.
    Siegel, G., Emden, J., Schnalke, F., Walter, A., Rückborn, K., and Wagner, K. G., 1991, Wirkungen von Knoblauch auf die Gefäß regulation, Med. Welt. 7a: 32–34.Google Scholar
  25. 25.
    Siegel, G., Grote, J., Schnalke, F., and Zimmer, K., 1989, The significance of the endothelium for hypoxic vasodilatation, Z. Kardiol. 78 [Suppl. 6]: 124–131.PubMedGoogle Scholar
  26. 26.
    Siegel, G., Jäger, R., Nolte, J., Bertsche, O., Roedel, H., and Schröter, R., 1974, Ionic concentrations and membrane potential in cerebral and extracerebral arteries, in: “Pathology of Cerebral Microcirculation”, J. Cervós-Navarro, ed., Walter de Gruyter, Berlin New York, pp 96–120.Google Scholar
  27. 27.
    Siegel, G., Kämpe, Ch., and Ebeling, B. J., 1981, pH-dependent myogenic control in cerebral vascular smooth muscle, in: “Cerebral Microcirculation and Metabolism”, J. Cervós-Navarro, E. Fritschka, eds., Raven Press, New York, pp 213–226.Google Scholar
  28. 28.
    Siegel, G., Mironneau, J., Schnalke, F., Schröder, G., Schulz, B.-G., and Grote, J., 1990, Vasodilatation evoked by K+ channel opening, Prog. Clin. Biol. Res. 327:299–306.PubMedGoogle Scholar
  29. 29.
    Siegel, G., Roedel, H., Nolte, J., Hofer, H. W., and Bertsche, O., 1976, Ionic composition and ion exchange in vascular smooth muscle, in: “Physiology of Smooth Muscle”, E. Bülbring, M. F. Shuba, eds., Raven Press, New York, pp 19–39.Google Scholar
  30. 30.
    Siegel, G., Stock, G., Schnalke, F., and Litza, B., 1987, Electrical and mechanical effects of prostacyclin in the canine carotid artery, in: “Prostacyclin and Its Stable Analogue Iloprost”, R. J. Gryglewski, G. Stock, eds., Springer-Verlag, Berlin Heidelberg New York London Paris Tokyo, pp 143–149.CrossRefGoogle Scholar
  31. 31.
    Siegel, G., Walter, A., Bostanjoglo, M., Jans, A. W. H., Kinne, R., Piculell, L., and Lindman, B., 1989, Ion transport and cation-polyanion interactions in vascular biomembranes, J. Membrane Sci. 41:353–375.CrossRefGoogle Scholar
  32. 32.
    Siegel, G., Wenzel, K., Schnalke, F., Mironneau, J., Schultz, G., Schröder, G., Schillinger, E., Grauhan, O., and Hetzer, R., 1990, Prostacyclin analogues as K+ channel openers, Clin. Pharmacol. 7:72–96.Google Scholar
  33. 33.
    Sperelakis, N., and Ohya, Y., 1990, Cyclic nucleotide regulation of Ca2+ slow channels and neurotransmitter release in vascular muscle, Prog. Clin. Biol. Res. 327:277–298.PubMedGoogle Scholar
  34. 34.
    Weston, A. H., 1990, The pharmacology of smooth muscle potassium channels, Clin. Pharmacol. 7:1–18.Google Scholar
  35. 35.
    Weston, A. H., 1990, in: “Cicletanine and K+ Channel Opening”, Institut Henri Beaufour, Le Plessis-Robinson, France.Google Scholar
  36. 36.
    Weston, A. H., and Abbott, A., 1987, New class of antihypertensive acts by opening K+ channels, Trends Pharmacol. Sci. 8:283–284.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • G. Siegel
    • 1
  • J. Emden
    • 1
  • K. Wenzel
    • 1
  • J. Mironneau
    • 2
  • G. Stock
    • 3
  1. 1.Institute of Physiology, Biophysical Research GroupThe Free University of BerlinBerlin 33Germany
  2. 2.Laboratoire de Physiologie Cellulaire et Pharmacologie MoléculaireUniversité de Bordeaux IIBordeauxFrance
  3. 3.Cardiovascular PharmacologyResearch Laboratories of Schering AGBerlin 65Germany

Personalised recommendations