Hypertrophy of colonic smooth muscle: contractile proteins, shortening velocity, and regulation.
Smooth muscle in megacolon was studied in the lethal spotted mouse and its normal sibling. In megacolon, structural remodeling and a very large increase in total protein content are associated with some changes in the contractile protein isoform composition. 1) There is a higher actin concentration in megacolon, primarily caused by a larger proportion of gamma-isoforms. 2) There was no difference in myosin concentration or in SM1/SM2 heavy chains in megacolon and normal muscle contractile proteins. 3) Only LC17a essential light chain is present in both normal and megacolon. 4) The 25- to 50-kDa 5'-insert occurs in 15-20% of the myosin in normal colon, compared with 5- to 10-fold lower amounts in megacolon. In permeabilized muscles there was no significant difference in unloaded shortening velocity (Vo) with maximal thiophosphorylation of the 20-kDa light chains, nor was there significant difference in the force vs. Ca2+ and force vs. myosin light chain phosphorylation relationships. At approximately 60% myosin light chain phosphorylation after Ca2+ activation, Vo of megacolon was approximately two times faster than Vo of normal muscle. These cellular changes largely account for the higher propulsive velocity of the colon in situ. The distribution of myosin and actin isoforms and the lack of a simple relationship between myosin light chain phosphorylation and Vo point to the operation of additional regulatory processes.
Siegman
M J
MJ
Department of Physiology, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Butler
T M
TM
Mooers
S U
SU
Trinkle-Mulcahy
L
L
Narayan
S
S
Adam
L
L
Chacko
S
S
Haase
H
H
Morano
I
I
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D003106:Colon / Q000473:pathology* / Q000502:physiology / Q000503:physiopathology*; D003285:Contractile Proteins / Q000096:biosynthesis*; D006579:Heterozygote; D006720:Homozygote; D006984:Hypertrophy; D008531:Megacolon / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008817:Mice, Mutant Strains; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000473:pathology* / Q000502:physiology / Q000503:physiopathology*; D018995:Myosin Heavy Chains / Q000096:biosynthesis; D009218:Myosins / Q000096:biosynthesis*; D010766:Phosphorylation; D012016:Reference Values
D000199:Actins; D003285:Contractile Proteins; D018995:Myosin Heavy Chains; D009218:Myosins