The Journal of Membrane Biology

, Volume 59, Issue 1, pp 19–25 | Cite as

Evidence for two separate Ca2+ pathways in smooth muscle plasmalemma

  • Kaushik D. Meisheri
  • O. Hwang
  • Cornelis van Breemen


The activation of rabbit aortic smooth muscle was studied by two most widely used vascular smooth muscle stimulants: α-adrenoceptor activation by norepinephrine (NE) and high-K+ depolarization. This was studied by measurements of isometric contractions and net as well as unidirectional Ca2+ fluxes. These parameters showed markedly differential sensitivities towards two smooth muscle inhibitors used in this study: D 600 and amrinone. By choosing an appropriate concentration of D 600 or amrinone, Ca2+ uptake or Ca2+ influx induced by high K+ or NE could be selectively inhibited. Furthermore, by using unidirectional flux measurements it was demonstrated that Ca2+ influx stimulated by NE and high K+ were additive in nature. The data from the addivity experiment exclude the interpretation of a common Ca2+ pathway with two separate mechanisms for opening it. The data on three criteria employed in this study provide evidence for the existence of two independent Ca2+ pathways, one for each mode of activation, for Ca2+ influx known to be associated with these contractions.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bolton, T.B. 1979. Mechanism of action of transmitters and other substances on smooth muscle.Physiol. Rev. 59:606Google Scholar
  2. Bose, D., Innes, I.R. 1975. Utilization of calcium pools during pharmaco- or electromechanical coupling in smooth muscle.Can. J. Physiol. Pharmacol. 53:586Google Scholar
  3. Breemen, C. van 1969. Blockade of membrane calcium fluxes by lanthanum in relation to vascular smooth muscle contractility.Arch. Int. Physiol. Biochim. 77:710Google Scholar
  4. Breeman, C. van 1975. Transmembrane calcium transport in vascular smooth muscle.In: Vascular Neuroeffector Mechanisms, 2nd International Symposium (Odense). pp. 67–79. Krager, Basel 67-79Google Scholar
  5. Breemen, C. van, Aaronson, P., Loutzenhiser, R. 1979. Na+, Ca2+ interactions in mammalian smooth muscle.Pharmacol. Rev. 30:167Google Scholar
  6. Breemen, C. van, Siegel, B. 1980 The mechanism of α-adrenergic activation of the dog coronary artery.Circ. Res. 46:426Google Scholar
  7. Deth, R., Breemen, C. van 1974. Relative contributions of Ca2+ influx and cellular Ca2+ release during drug induced activation of the rabbit aorta.Pfluegers Arch. 348:13Google Scholar
  8. Deth, R., Breemen, C. van 1977. Agonist induced release of intracellular Ca2+ in the rabbit aorta.J. Membrane Biol. 30:363Google Scholar
  9. Farah, A.F., Alousi, A.A. 1978. New cardiotonic agents: A search for digitalis substitute.Life Sci. 22:1139Google Scholar
  10. Fleckenstein, A. 1977. Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle.Annu. Rev. Pharmacol. 17:149Google Scholar
  11. Hille, B. 1973. Potassium channels in myelinated nerve. Selective permeability to small cations.J. Gen. Physiol. 61:669Google Scholar
  12. Hinke, J.A.M. 1965. Calcium requirements for noradrenaline and high potassium ion contraction in arterial smooth muscle.In: Muscle. W.M. Paul, E.E. Daniel, C.M. Kay, and G. Monckton, editors. p. 269. Pergamon Press, OxfordGoogle Scholar
  13. Hudgins, P.M., Weiss, G.B. 1968. Differential effects of calcium removal upon vascular smooth muscle contraction induced by norepinephrine, histamine, and potassium.J. Pharmacol. Exp. Ther. 159:91Google Scholar
  14. Kalsner, S., Nickerson, M., Boyd, G. 1970. Selective blockade of potassium-induced contractions of aortic strips by β-diethylaminoethyldiphenylpropylacetate (SKF 525A).J. Pharmacol. Exp. Ther. 174:500Google Scholar
  15. Meisheri, K.D., Hwang, O., Breemen, C. van 1980b. Norepinephrine and high-K+ depolarization utilize separate Ca2+ channels during vascular smooth muscle activation.Fed. Proc. 39:711Google Scholar
  16. Meisheri, K.D., Palmer, R.F., Breemen, C. van 1980a. The effects of amrinone on contractility, Ca2+ uptake, and cAMP in smooth muscle.Eur. J. Pharmacol. 61:159Google Scholar
  17. Ritchie, J.M. 1975. Binding of tetrodotoxin and saxitoxin to sodium channels.Phil. Trans. R. Soc. London B 270:319Google Scholar
  18. Waugh, W.H. 1962. Role of calcium in contractile excitation of vascular smooth muscle by epinephrine and potassium.Circ. Res. 11:927Google Scholar

Copyright information

© Springer-Verlag New York Inc 1981

Authors and Affiliations

  • Kaushik D. Meisheri
    • 1
  • O. Hwang
    • 1
  • Cornelis van Breemen
    • 1
  1. 1.Department of PharmacologyUniversity of Miami School of MedicineMiami

Personalised recommendations