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The 3-state model of muscle regulation revisited: is a fourth state involved?

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Abstract

The 3-state model of muscle regulation has been useful in explaining the roles of Ca2+ and myosin heads in activation and relaxation of striated muscle contraction. However, there are some phenomena, which cannot simply be explained by the 3-state model. These include increased Ca2+-binding caused by strong-binding myosin heads and residual active force at low Ca2+ in the case of familial hypertrophic cardiomyopathy. Here, I review experimental data which provide evidence for an additional state, a myosin-induced Open state present in the absence of Ca2+ (Open−Ca2+) which like the normal Open+Ca2+ state, is an active state and can allow myosin heads to cycle and generate force. A schematic diagram is presented which shows that the formation of the Open−Ca2+ state is on a parallel path with the formation of the Open+Ca2+ state and can contribute to activation.

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Acknowledgments

I greatly appreciate input on drafts of this review and helpful critical discussions with my colleagues, Drs. Franklin Fuchs, Michael Geeves, and Zenon Grabarek. Support from NIH HL9116 is also acknowledged.

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Authors and Affiliations

  1. Cardiovascular Program, Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA, 02472, USA

    Sherwin S. Lehrer

  2. Department of Neurology, Harvard Medical School, Boston, MA, USA

    Sherwin S. Lehrer

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  1. Sherwin S. Lehrer
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Correspondence to Sherwin S. Lehrer.

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Lehrer, S.S. The 3-state model of muscle regulation revisited: is a fourth state involved?. J Muscle Res Cell Motil 32, 203–208 (2011). https://doi.org/10.1007/s10974-011-9263-8

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