Key result
SMB myosin heavy chain knockout with compensatory increase in SMA MHC protein resulted in enhanced sustained KPSS-induced tonic contraction and a reduced rate of force generation in phasic tissues.
Why the study?
Does SMB MHC knockout alter tonic contraction and rate of force generation in smooth muscle tissues in mice?
Does SMB MHC knockout alter tonic contraction and rate of force generation in smooth muscle tissues in mice?
Removing SMB MHC protein expression with a compensatory increase in SMA MHC protein enhances sustained KPSS-induced tonic contraction and reduces the rate of force generation in phasic smooth muscle tissues.
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.
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Huang et al. (2012) studied Healthy (wild-type vs SMB knockout). SMB myosin heavy chain knockout vs. Wild-type mice was evaluated on Sustained tonic force (area under the curve from peak force to 10 min after peak force) in ileum with KPSS stimulation (p=0.017). SMB myosin heavy chain knockout with compensatory increase in SMA MHC protein resulted in enhanced sustained KPSS-induced tonic contraction and a reduced rate of force generation in phasic tissues.
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