Faculty Collaboration Database

SMB myosin heavy chain knockout enhances tonic contraction and reduces the rate of force generation in ileum and stomach antrum. Am J Physiol Cell Physiol 2013 Jan 15;304(2):C194-206

Date

11/09/2012

Pubmed ID

23135699

Pubmed Central ID

PMC3546810

DOI

10.1152/ajpcell.00280.2012

Scopus ID

2-s2.0-84872387287 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

The role of SMA and SMB smooth muscle myosin heavy chain (MHC) isoforms in tonic and phasic contractions was studied in phasic (longitudinal ileum and stomach circular antrum) and tonic (stomach circular fundus) smooth muscle tissues of SMB knockout mice. Knocking out the SMB MHC gene eliminated SMB MHC protein expression and resulted in upregulation of the SMA MHC protein without altering the total MHC protein level. Switching from SMB to SMA MHC protein expression decreased the rate of the force transient and increased the sustained tonic force in SMB((-/-)) ileum and antrum with high potassium (KPSS) but not with carbachol (CCh) stimulation. The increased tonic contraction under the depolarized condition was not through changes in second messenger signaling pathways (PKC/CPI-17 or Rho/ROCK signaling pathway) or LC(20) phosphorylation. Biochemical analyses showed that the expression of contractile regulatory proteins (MLCK, MLCP, PKCδ, and CPI-17) did not change significantly in tissues tested except for PKCα protein expression being significantly decreased in the SMB((-/-)) antrum. However, specifically activating PKCα with phorbol dibutyrate (PDBu) was not significantly different in knockout and wild-type tissues, with total force being a fraction of the force generation with KPSS or CCh stimulation in SMB((-/-)) ileum and antrum. Taken together, these data show removing the SMB MHC protein expression with a compensatory increase in the SMA MHC protein results in enhanced sustained KPSS-induced tonic contraction with a reduced rate of force generation in these phasic tissues.

Author List

Huang Q, Babu GJ, Periasamy M, 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
Carbachol
Cholinergic Agonists
Ileum
Mice
Mice, Knockout
Muscle Contraction
Muscle Strength
Muscle, Smooth
Myosin Heavy Chains
Phorbol 12,13-Dibutyrate
Phosphorylation
Potassium
Protein Kinase C-alpha
Pyloric Antrum
Second Messenger Systems
Smooth Muscle Myosins