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Smooth-muscle contraction without smooth-muscle myosin

Nature Cell Biology volume 2, pages 371–375 (2000)Cite this article

Abstract

Here we have used gene-targeting to eliminate expression of smooth-muscle myosin heavy chain. Elimination of this gene does not affect expression of non-muscle myosin heavy chain, and knockout individuals typically survive for three days. Prolonged activation, by KCl depolarisation, of intact bladder preparations from wild-type neonatal mice produces an initial transient state (phase 1) of high force generation and maximal shortening velocity, which is followed by a sustained state (phase 2) characterized by low force generation and maximal shortening velocity. Similar preparations from knockout neonatal mice do not undergo phase 1, but exhibit a normal phase 2. We propose that, in neonatal smooth muscle phase 1 is generated by recruitment of smooth-muscle myosin heavy chain, whereas phase 2 can be generated by activation of non-muscle myosin heavy chain. We conclude that phase 1 becomes indispensable for survival and normal growth soon after birth, particularly for functions such as homeostasis and circulation.

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Figure 1: Targeted disruption of the SM-MHC gene.
Figure 2: Comparison of wild-type and knockout mice.
Figure 3: Expression of MHCs.
Figure 4: Patterns of force generation in wild-type and SM-MHC-deficient smooth muscle.
Figure 5: Presence of NM-MHC in wild-type and knockout smooth-muscle cells.
Figure 6: Presence of SM-MHC in wild-type and knockout smooth-muscle cells.
Figure 7: Relationship between phase-2 force generation and expression of NM-MHC.
Figure 8: Bladder and heart histologies of wild-type and knockout mice.

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Acknowledgements

We thank T. Walther for technical help, D. Balzereit for technical assistance, and C. Grund and W. Franke for help with tissue preparations. This work was supported by grant Mo 362/16-2 from the Deutsche Forschungsgemeinschaft to I.M. and M.B.

Correspondence and requests for materials should be addressed to I.M. or M.B.

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Author notes

  1. Gui-Xuan Chai and Leonidas G. Baltas: These authors contributed equally to this work

Authors and Affiliations

  1. Max Delbrück Center for Molecular Medicine (MDC), Robert-Rössle-Strabe 10, Berlin, D-13092, Germany

    Ingo Morano, Gui-Xuan Chai, Leonidas G. Baltas, Valeria Lamounier-Zepter, Gudrun Lutsch, Monika Kott, Hannelore Haase & Michael Bader

  2. Department of Physiology, Humboldt University (Charité), Berlin, D-10117, Germany

    Ingo Morano

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Morano, I., Chai, GX., Baltas, L. et al. Smooth-muscle contraction without smooth-muscle myosin . Nat Cell Biol 2, 371–375 (2000). https://doi.org/10.1038/35014065

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