Smooth muscle myosin: regulation and properties.
The relationship of the biochemical states to the mechanical events in contraction of smooth muscle cross-bridges is reviewed. These studies use direct measurements of the kinetics of Pi and ADP release. The rate of release of Pi from thiophosphorylated cycling cross-bridges held isometric was biphasic with turnovers of 1.8 s-1 and 0.3 s-1, reflecting properties and forces directly acting on cross-bridges through mechanisms such as positive strain and inhibition by high-affinity MgADP binding. Fluorescent transients reporting release of an ADP analogue 3'-deac-edaADP were significantly faster in phasic than in tonic smooth muscles. Thiophosphorylation of myosin regulatory light chains (RLCs) increased and positive strain decreased the release rate around twofold. The rates of ADP release from rigor cross-bridges and the steady-state Pi release from cycling isometric cross-bridges are similar, indicating that the ADP-release step or an isomerization preceding it may limit the ATPase rate. Thus ADP release in phasic and tonic smooth muscles is a regulated step with strain- and dephosphorylation-dependence. High affinity of cross-bridges for ADP and slow ADP release prolong the fraction of the duty cycle occupied by strongly bound AM.ADP state(s) and contribute to the high economy of force that is characteristic of smooth muscle. RLC thiophosphorylation led to structural changes in smooth muscle cross-bridges consistent with our findings that thiophosphorylation and strain modulate product release.
Somlyo
Avril V
AV
Molecular Physiology and Biological Physics, University of Virginia, PO Box 800736, 1300 Jefferson Park Avenue, Charlottesville, VA 22908-0736, USA. avs5u@virginia.edu
Khromov
Alexander S
AS
Webb
Martin R
MR
Ferenczi
Michael A
MA
Trentham
David R
DR
He
Zhen-He
ZH
Sheng
Sitong
S
Shao
Zhifeng
Z
Somlyo
Andrew P
AP
D000199:Actins / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D007700:Kinetics; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D009218:Myosins / Q000378:metabolism / Q000502:physiology*; D010710:Phosphates / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding
D000199:Actins; D010710:Phosphates; D000244:Adenosine Diphosphate; D009218:Myosins