Abstract
PHOSPHORYLATION of myosin light chains by a calmodulin-myosin light-chain kinase (MLCK) pathway is considered to be responsible for coupling increased calcium concentration with contraction in smooth muscle1,2. This simple view has, however, recently been questioned3–6. To test this hypothesis directly, we microinjected individual smooth muscle cells with modulators of the MLCK pathway while measuring contraction and calcium-ion concentration. Injection of a constitutively active proteolysed form of MLCK causes contraction but no change in calcium concentra-tion. By contrast, injection of peptide inhibitors of MLCK blocks contraction in response to K+ depolarization, despite the fact that the change in calcium concentration in response to stimulation was enhanced over controls. These results provide a direct demonstration at the level of a single cell that activation of the calmodulin–MLCK pathway is both necessary and sufficient to trigger contraction of smooth muscle.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Somlyo, A. P. Circulation Res. 57, 497–507 (1985).
Adelstein, R. S. & Eisenberg, E. A. Rev. Biochem. 44, 921–956 (1980).
Kamm, K. E. & Stull, J. T. A. Rev. Pharmacol. Toxicol. 25, 593–620 (1985).
Walsh, M. P. in Regulation and Contraction of Smooth Muscle (eds Siegman, M. J., Somlyo, A P. & Stephens, N. L.) 119–141 (Liss, New York, 1987).
Dillon, P. F., Aksoy, M. O., Driska, S. P. & Murphy, R. A. Science 211, 495–497 (1981).
Siegman, M. J., Butler, T. M., Mooers, S. U. & Michalek, A. Pflügers Arch. ges. Physiol. 401, 385–390 (1984).
Fay, F. S., Hoffman, R., LeClaire, S. & Merriam, P. Meth. Enzym. 85, 284–292 (1982).
Yagi, S., Becker, P. L. & Fay, F. S. Proc. natn. Acad. Sci. U.S.A. 85, 4109–4113 (1988).
Williams, D. A., Fogarty, K. E., Tsien, R. Y. & Fay, F. S. Nature 318, 558–561 (1986).
Williams, D. A., Becker, P. L. & Fay, F. S. Science 235, 1644–1648 (1987).
Becker, P. L. & Fay, F. S. Am. J. Physiol. 253, C613–C618 (1987).
Ikebe, M., Stepinska, M., Kemp, B. E., Means, A. R. & Hartshorne, D. J. J. biol. Chem. 262, 13828–13834 (1987).
Pearson, R. B., Wettenhall, R. E. H., Means, A. R., Hartshorne, D. J. & Kemp, B. E. Science 241, 970–973 (1988).
Kemp, B. E., Pearson, R. B., Guerieco Jr, V., Baguchi, I. C. & Means, A. R. J. biol. Chem. 262, 2542–2548 (1987).
Lukas, T. J., Burgess, W. H., Prendergast, F. G., Lau, W. & Watterson, D. M. Biochemistry 25, 1458–1464 (1986).
Ikebe, M., Kemp, B. E. & Hartshorne, D. J. Biophys. J. 53, 182a (1988).
Fay, F. S. & Delise, C. M. Proc. natn. Acad. Sci. U.S.A. 70, 641–645 (1973).
Grynkievicz, G., Poenie, M. & Tsien, R. Y. J. biol. Chem. 260, 3440–3450 (1985).
Kargacin, G. J. & Fay, F. S. J. gen. Physiol. 90, 49–73 (1987).
Ikebe, M. & Hartshorne, D. J. J. biol. Chem. 260, 13146–13153 (1985).
Ikebe, M. & Hartshorne, D. J. Biochemistry 24, 2380–2386 (1985).
Walsh, M. P., Hinkins, S., Dabrowska, R. & Hartshorne, D. J. Meth. Enzym. 99, 279–288 (1988).
Fay, F. S. & Singer, J. J. Am. J. Physiol. 232, C144–C154 (1977).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Itoh, T., Ikebe, M., Kargacin, G. et al. Effects of modulators of myosin light-chain kinase activity in single smooth muscle cells. Nature 338, 164–167 (1989). https://doi.org/10.1038/338164a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/338164a0
This article is cited by
-
Sevoflurane and isoflurane inhibit KCl-induced Class II phosphoinositide 3-kinase α subunit mediated vasoconstriction in rat aorta
BMC Anesthesiology (2015)
-
Cellular and molecular mechanisms regulating vascular tone. Part 2: regulatory mechanisms modulating Ca2+ mobilization and/or myofilament Ca2+ sensitivity in vascular smooth muscle cells
Journal of Anesthesia (2007)
-
Cellular and molecular mechanisms regulating vascular tone. Part 1: basic mechanisms controlling cytosolic Ca2+ concentration and the Ca2+-dependent regulation of vascular tone
Journal of Anesthesia (2007)
-
A major role for the Rho‐associated coiled coil forming protein kinase in G‐protein‐mediated Ca2+ sensitization through inhibition of myosin phosphatase in rabbit trachea
British Journal of Pharmacology (1999)
-
Signal transduction and regulation in smooth muscle
Nature (1994)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
