Mijailovich, Butler, Fredburg, 2000

Model Status

This is the original unchecked version of the model imported from the previous CellML model repository, 24-Jan-2006.

Model Structure

The tidal action of breathing continually places load fluctuations on the smooth muscle of the lungs. Similary, the pulsatile flow of blood through the arteries and arterioles places load fluctuations on the walls of the vasculature. Smooth muscles in the urethra, urinary bladder, and the gastrointestinal tract are also exposed to periodic stretch. In summary, oscillations in smooth muscle load are an inherent part of smooth muscle physiology.

On May 22, 1954 two papers in Nature (Huxley, A.F. & Niedergerke, R., Nature 173, 971-973, 1954 PubMed ID: 13165697; and ; Huxley, H.E. & Hanson, J., Nature 173, 973-976, 1954 ) were published. These articles outline the foundation of the sliding filament hypothesis of muscle contraction, which proposes that when skeletal (or cardiac) muscle contracts, the thin (actin) and thick (myosin) filaments in each sarcomere slide along relative to each other without their shortening, thickening, or folding. The strength of the relative motion between the thick and thin filaments is determined by the number of cross-bridges that can form between the two.

In 1988, Hai and Murphy published two papers (Hai and Murphy, American Journal of Physiology 255, C86-C94, 1988, and C401-7, 1988) which describe the regulation of shortening velocity by cross-bridge phosphorylation in smooth muscle, and a latch regulatory scheme for Ca2+-dependent smooth muscle activation, respectively. Please see the figure below for more details of this model.

In the Mijailovich et al. 2000 publication described here, the authors combine the ideas of Hukley with those of Hai and Murphy, and they develop an integrated model of smooth muscle contraction. They refer to this combined model as the HHM theory, and they use this model to analyse, in particular, the myosin bond length distributions. They study how these distributions are influenced by periodic changes in the muscle length, and how these changes in bond length lead to changes in muscle mechanics and the rate of ATP consumption. The model may be applied to help understand why airway narrowing is limited in healthy lungs, but it can become excessive in asthmatic lungs.

The complete original paper reference is cited below:

Perturbed Equilibria of Myosin Binding in Airway Smooth Muscle: Bond-Length Distributions, Mechanics, and ATP Metabolism, Srboljub M. Mijailovich, James P. Butler, and Jeffrey J. Fredberg, 2000, Biophysical Journal , 79, 2667-2681. (Full text (HTML) and PDF versions of the article are available to subscibers on the Biophysical Journal website.) PubMed ID: 11053139

Hai and Murphy's four-state model: the latch regulatory scheme for Ca2+-dependent smooth muscle activation and Huxley's slidin filament model. A represents the actin filament, M represents detached myosin, Mp is detached, phosphorylated myosin, AM is the actin-myosin complex, and AMp is the phosphorylated actin-myosin complex.