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MUSCLE CELL BIOLOGY AND CELL MOTILITY

Phospholamban knockout increases CaM kinase II activity and intracellular Ca²⁺ wave activity and alters contractile responses of murine gastric antrum

Department of Physiology and Cell Biology, Center of Biomedical Research Excellence, University of Nevada School of Medicine, Reno, Nevada

Submitted 13 September 2007 ; accepted in final form 28 November 2007

Phospholamban (PLB) inhibits the sarcoplasmic reticulum (SR) Ca²⁺-ATPase (SERCA), and this inhibition is relieved by Ca²⁺ calmodulin-dependent protein kinase II (CaM kinase II) phosphorylation. We previously reported significant differences in contractility, SR Ca²⁺ release, and CaM kinase II activity in gastric fundus smooth muscles as a result of PLB phosphorylation by CaM kinase II. In this study, we used PLB-knockout (PLB-KO) mice to directly examine the effect of PLB absence on contractility, CaM kinase II activity, and intracellular Ca²⁺ waves in gastric antrum smooth muscles. The frequencies and amplitudes of spontaneous phasic contractions were elevated in antrum smooth muscle strips from PLB-KO mice. Bethanecol increased the amplitudes of phasic contractions in antrum smooth muscles from both control and PLB-KO mice. Caffeine decreased and cyclopiazonic acid (CPA) increased the basal tone of antrum smooth muscle strips from PLB-KO mice, but the effects were less pronounced compared with control strips. The CaM kinase II inhibitor KN-93 was less effective at inhibiting caffeine-induced relaxation in antrum smooth muscle strips from PLB-KO mice. CaM kinase II autonomous activity was elevated, and not further increased by caffeine, in antrum smooth muscles from PLB-KO mice. Similarly, the intracellular Ca²⁺ wave frequency was elevated, and not further increased by caffeine, in antrum smooth muscles from PLB-KO mice. These findings suggest that PLB is an important modulator of gastric antrum smooth muscle contractility by modulation of SR Ca²⁺ release and CaM kinase II activity.

gastrointestinal smooth muscle; Ca²⁺ calmodulin-dependent protein kinase II

This article has been cited by other articles:

				M. Kim, G. W. Hennig, K. Park, I. S. Han, T. K. Smith, S. D. Koh, and B. A. Perrino Modulation of murine gastric antrum smooth muscle STOC activity and excitability by phospholamban J. Physiol., October 15, 2008; 586(20): 4977 - 4991. [Abstract] [Full Text] [PDF]