Forced expression of essential myosin light chain isoforms demonstrates their role in smooth muscle force production.
The molecular determinants of the contractile properties of smooth muscle are poorly understood, and have been suggested to be controlled by splice variant expression of the myosin heavy chain near the 25/50-kDa junction (Kelley, C. A., Takahashi, M., Yu, J. H., and Adelstein, R. S. (1993) J. Biol. Chem. 268, 12848-12854) as well as by differences in the expression of an acidic (MLC(17a)) and a basic (MLC(17b)) isoform of the 17-kDa essential myosin light chain (Nabeshima, Y., Nonomura, Y., and Fujii-Kuriyama, Y. (1987) J. Biol. Chem. 262, 106508-10612). To investigate the molecular mechanism that regulates the mechanical properties of smooth muscle, we determined the effect of forced expression of MLC(17a) and MLC(17b) on the rate of force activation during agonist-stimulated contractions of single cultured chicken embryonic aortic and gizzard smooth muscle cells. Forced expression of MLC(17a) in aortic smooth muscle cells increased (p < 0.05) the rate of force activation, forced expression of MLC(17b) in gizzard smooth muscle cells decreased (p < 0.05) the rate of force activation, while forced expression of the endogenous MLC(17) isoform had no effect on the rate of force activation. These results demonstrate that MLC(17) is a molecular determinant of the contractile properties of smooth muscle. MLC(17) could affect the contractile properties of smooth muscle by either changing the stiffness of the myosin lever arm or modulating the rate of a load-dependent step and/or transition in the actomyosin ATPase cycle.
Huang
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Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-5038, USA.
Fisher
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Brozovich
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D000818:Animals; D001011:Aorta / Q000166:cytology; D002642:Chick Embryo; D005895:Gizzard, Avian / Q000166:cytology; D007700:Kinetics; D009119:Muscle Contraction / Q000235:genetics; D009130:Muscle, Smooth / Q000196:embryology / Q000378:metabolism*; D018994:Myosin Light Chains / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic; D014159:Transducers; D014162:Transfection
D018994:Myosin Light Chains; D020033:Protein Isoforms