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Myosin Regulatory Light Chain Phosphorylation and Strain Modulate Adenosine Diphosphate Release from Smooth Muscle Myosin

Alexander S. Khromov ^*, Martin R. Webb , Michael A. Ferenczi , David R. Trentham , Andrew P. Somlyo ^* and Avril V. Somlyo ^*

^* Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908 USA; National Institute for Medical Research, London NW7 1AA, United Kingdom; and Biomedical Sciences Division, Imperial College, London SW7 2AZ, United Kingdom

Correspondence: Address reprint requests to Avril V. Somlyo, PhD, PO Box 800736, 1300 Jefferson Park Ave., Charlottesville, VA 22908-0736. Tel.: 434-924-5926; Fax: 434-982-1616; E-mail: avs5u{at}virginia.edu.

The effects of myosin regulatory light chain (RLC) phosphorylation and strain on adenosine diphosphate (ADP) release from cross-bridges in phasic (rabbit bladder (Rbl)) and tonic (femoral artery (Rfa)) smooth muscle were determined by monitoring fluorescence transients of the novel ADP analog, 3'-deac-eda-ADP (deac-edaADP). Fluorescence transients reporting release of 3'-deac-eda-ADP were significantly faster in phasic (0.57 ± 0.06 s^-1) than tonic (0.29 ± 0.03 s^-1) smooth muscles. Thiophosphorylation of regulatory light chains increased and strain decreased the release rate twofold. The calculated (k_-ADP/k_+ADP) dissociation constant, K_d of unstrained, unphosphorylated cross-bridges for ADP was 0.6 µM for rabbit bladder and 0.3 µM for femoral artery. The rates of ADP release from rigor bridges and reported values of P_i release (corresponding to the steady-state adenosine triphosphatase (ATPase) rate of actomyosin (AM)) from cross-bridges during a maintained isometric contraction are similar, indicating that the ADP-release step or an isomerization preceding it may be limiting the adenosine triphosphatase rate. We conclude that the strain- and dephosphorylation-dependent high affinity for and slow ADP release from smooth muscle myosin prolongs the fraction of the duty cycle occupied by strongly bound actomyosin.ADP state(s) and contributes to the high economy of force.

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