Regulation of the Ca2+-Force Relationship in Permeabilized Arterial Smooth Muscle

  • Junji Nishimura
  • Suzanne Moreland
  • Robert S. Moreland
  • Cornelis van Breemen
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 304)


It is generally accepted that the primary trigger for smooth muscle contraction is the elevation of intracellular Ca2+ concentration ([Ca2+]i) and subsequent phosphorylation of myosin light chain (MLC) by the Ca2+-calmodulin dependent MLC kinase (for reviews see Kamm and Stull, 1985; Somlyo, 1985). However, simultaneous measurements of tension and [Ca2+]i in intact tissues have shown that during continuous stimulation, although a-adrenergic agonist induced force is maintained at high constant levels, [Ca2+]i falls close to basal concentrations (Morgan and Morgan, 1982; 1984a). It has also been demonstrated that levels of both MLC phosphorylation and shortening velocity fall to suprabasal levels during the phase of force maintenance in intact smooth muscle (Dillon et al., 1981). In order to account for these phenomena, a high Ca2+ sensitivity state, the latch state, was proposed to be important for the maintenance of developed force in the face of significant decreases in the [Ca2+]i and levels of MLC phosphorylation (Dillon et al., 1981). Similar phenomena, increases in the Ca2+-force relationship, have been demonstrated in skinned smooth muscle preparations by the addition of exogenous calmodulin (Cassidy et al., 1981; Rüegg and Paul, 1982), an initial stimulation in high [Ca2+] followed by exposure to a lower [Ca2+] (Chatterjee and Murphy, 1981; Moreland and Murphy, 1986), and stimulation by phorbol esters (Chatterjee and Tajeda, 1986; Itoh et al., 1988) or GTPγS (Fujiwara et al., 1989). However, until recently it has not been possible to increase the Ca2+ sensitivity of force by a physiological mode of stimulation. Recent studies utilizing the Staphylcoccal α-toxin permeabilized smooth muscle preparation have shown that receptor stimulation by a physiological agonist plus GTP can produce a significant level of additional force, at a fixed submaximal [Ca2+], as compared to the force developed in response to Ca2+ alone (Nishimura et al., 1988; Kitazawa et al., 1989; Kobavashi et al., 1989).


Myosin Light Chain Smooth Muscle Contraction Smooth Muscle Tissue Force Relationship Smooth Muscle Preparation 
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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Junji Nishimura
    • 1
  • Suzanne Moreland
    • 2
    • 3
  • Robert S. Moreland
    • 3
  • Cornelis van Breemen
    • 1
  1. 1.Department of Molecular and Cellular PharmacologyUniversity of Miami, School of MedicineMiamiUSA
  2. 2.Department of PharmacologyBristol-Myers Squibb Pharmaceutical Research InstitutePrincetonUSA
  3. 3.Bockus Research InstituteGraduate HospitalPhiladelphiaUSA

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