Isoform switching from SM-B to SM-A myosin results in decreased contractility and altered expression of thin filament regulatory proteins.
We previously generated an isoform-specific gene knockout mouse in which SM-B myosin is permanently replaced by SM-A myosin. In this study, we examined the effects of SM-B myosin loss on the contractile properties of vascular smooth muscle, specifically peripheral mesenteric vessels and aorta. The absence of SM-B myosin leads to decreased velocity of shortening and increased isometric force generation in mesenteric vessels. Surprisingly, the same changes occur in aorta, which contains little or no SM-B myosin in wild-type animals. Calponin and activated mitogen-activated protein kinase expression is increased and caldesmon expression is decreased in aorta, as well as in bladder. Light chain-17b isoform (LC(17b)) expression is increased in aorta. These results suggest that the presence or absence of SM-B myosin is a critical determinant of smooth muscle contraction and that its loss leads to additional changes in thin filament regulatory proteins.
Babu
Gopal J
GJ
Dept. of Physiology and Cell Biology, Ohio State University College of Medicine, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA. periasamy.1@osu.edu
Pyne
Gail J
GJ
Zhou
Yingbi
Y
Okwuchukuasanya
Chris
C
Brayden
Joseph E
JE
Osol
George
G
Paul
Richard J
RJ
Low
Robert B
RB
Periasamy
Muthu
M
D000818:Animals; D001011:Aorta / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D002148:Calmodulin-Binding Proteins / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D018995:Myosin Heavy Chains / Q000502:physiology*; D020033:Protein Isoforms / Q000502:physiology; D024745:Smooth Muscle Myosins / Q000502:physiology*; D013152:Splanchnic Circulation / Q000502:physiology; D000096985:Calponins
D002135:Calcium-Binding Proteins; D002148:Calmodulin-Binding Proteins; D008840:Microfilament Proteins; D020928:Mitogen-Activated Protein Kinases; D018995:Myosin Heavy Chains; D020033:Protein Isoforms; D024745:Smooth Muscle Myosins; D000096985:Calponins