| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
TRANSLATIONAL PHYSIOLOGY
1Cardiovascular Division, Department of Internal Medicine, and 2Department of Molecular Physiology and Cellular Biophysics, University of Virginia, Charlottesville, Virginia 22908
Submitted 10 February 2004 ; accepted in final form 13 May 2004
ABSTRACT
Serine 19 phosphorylation of the myosin regulatory light chain (MRLC) appears to be the primary determinant of smooth muscle force development. The relationship between MRLC phosphorylation and force is nonlinear, showing that phosphorylation is not a simple switch regulating the number of cycling cross bridges. We reexamined the MRLC phosphorylation-force relationship in slow, tonic swine carotid media; fast, phasic rabbit urinary bladder detrusor; and very fast, tonic rat anococcygeus. We found a sigmoidal dependence of force on MRLC phosphorylation in all three tissues with a threshold for force development of 
0.15 mol Pi/mol MRLC. This behavior suggests that force is regulated in a highly cooperative manner. We then determined whether a model that employs both the latch-bridge hypothesis and cooperative activation could reproduce the relationship between Ser19-MRLC phosphorylation and force without the need for a second regulatory system. We based this model on skeletal muscle in which attached cross bridges cooperatively activate thin filaments to facilitate cross-bridge attachment. We found that such a model describes both the steady-state and time-course relationship between Ser19-MRLC phosphorylation and force. The model required both cooperative activation and latch-bridge formation to predict force. The best fit of the model occurred when binding of a cross bridge cooperatively activated seven myosin binding sites on the thin filament. This result suggests cooperative mechanisms analogous to skeletal muscle that will require testing.
modeling; myosin regulatory light chain; thin filament regulation; vascular smooth muscle
This article has been cited by other articles:
|
|
 |
|
  C. M. Rembold, A. D. Tejani, M. L. Ripley, and S. Han Paxillin phosphorylation, actin polymerization, noise temperature, and the sustained phase of swine carotid artery contraction Am J Physiol Cell Physiol, September 1, 2007; 293(3): C993 - C1002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Rembold Force suppression and the crossbridge cycle in swine carotid artery Am J Physiol Cell Physiol, September 1, 2007; 293(3): C1003 - C1009. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. H. Ratz, K. M. Berg, N. H. Urban, and A. S. Miner Regulation of smooth muscle calcium sensitivity: KCl as a calcium-sensitizing stimulus Am J Physiol Cell Physiol, April 1, 2005; 288(4): C769 - C783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Meeks, M. L. Ripley, Z. Jin, and C. M. Rembold Heat shock protein 20-mediated force suppression in forskolin-relaxed swine carotid artery Am J Physiol Cell Physiol, March 1, 2005; 288(3): C633 - C639. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Gu, G. D Thorne, R. L Wardle, Y. Ishida, and R. J Paul Ca2+-independent hypoxic vasorelaxation in porcine coronary artery J. Physiol., February 1, 2005; 562(3): 839 - 846. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. F. Dillon Dick Murphy: three decades as the touchstone of smooth muscle physiology. Focus on "Cooperative attachment of cross bridges predicts regulation of smooth muscle force by myosin phosphorylation" Am J Physiol Cell Physiol, September 1, 2004; 287(3): C590 - C591. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
