Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Tonic and phasic smooth muscle contraction is not regulated by the PKCα - CPI-17 pathway in swine stomach antrum and fundus. PLoS One 2013;8(9):e74608

Date

09/24/2013

Pubmed ID

24058600

Pubmed Central ID

PMC3776813

DOI

10.1371/journal.pone.0074608

Scopus ID

2-s2.0-84884260541 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

Regulation of myosin light chain phosphatase (MLCP) via protein kinase C (PKC) and the 17 kDa PKC-potentiated inhibitor of myosin light chain phosphatase (CPI-17) has been reported as a Ca(2+) sensitization signaling pathway in smooth muscle (SM), and thus may be involved in tonic vs. phasic contractions. This study examined the protein expression and spatial-temporal distribution of PKCα and CPI-17 in intact SM tissues. KCl or carbachol (CCh) stimulation of tonic stomach fundus SM generates a sustained contraction while the phasic stomach antrum generates a transient contraction. In addition, the tonic fundus generates greater relative force than phasic antrum with 1 µM phorbol 12, 13-dibutyrate (PDBu) stimulation which is reported to activate the PKCα - CPI-17 pathway. Western blot analyses demonstrated that this contractile difference was not caused by a difference in the protein expression of PKCα or CPI-17 between these two tissues. Immunohistochemical results show that the distribution of PKCα in the longitudinal and circular layers of the fundus and antrum do not differ, being predominantly localized near the SM cell plasma membrane. Stimulation of either tissue with 1 µM PDBu or 1 µM CCh does not alter this peripheral PKCα distribution. There are no differences between these two tissues for the CPI-17 distribution, but unlike the PKCα distribution, CPI-17 appears to be diffusely distributed throughout the cytoplasm under relaxed tissue conditions but shifts to a primarily peripheral distribution at the plasma membrane with stimulation of the tissues with 1 µM PDBu or 1 µM CCh. Results from double labeling show that neither PKCα nor CPI-17 co-localize at the adherens junction (vinculin/talin) at the membrane but they do co-localize with each other and with caveoli (caveolin) at the membrane. This lack of difference suggests that the PKCα - CPI-17 pathway is not responsible for the tonic vs. phasic contractions observed in stomach fundus and antrum.

Author List

Zhang Y, Hermanson ME, Eddinger TJ

Author

Thomas Eddinger PhD Bioological Sciences in the Biology department at Marquette University




MESH terms used to index this publication - Major topics in bold

Animals
Biomechanical Phenomena
Carbachol
Gastric Fundus
Muscle Contraction
Muscle, Smooth
Myosin-Light-Chain Phosphatase
Phorbol 12,13-Dibutyrate
Protein Kinase C-alpha
Pyloric Antrum
Signal Transduction
Sus scrofa