Activation of smooth muscle and theories of contraction

We have analyzed the behavior of a linear, cyclic, four state model of regulation of contraction of smooth muscle. The model involves twenty one parameters: sixteen rate constants, three initial conditions, and NT$\sb3$ and NT$\sb4$, where N is the number of crossbridges, and T$\sb3$ and T$\sb4$ are the tension of phosphorylated and dephosphorylated crossbridges, respectively. The mathematical solution, for any state, is made of the sum of three weighted exponentials plus a constant term. The parameters can be obtained if transients of phosphorylation and tension are obtained, at two different concentrations of ATP, at least, with known ADP and Pi. If only data at one concentration of ATP is available, the model can be identified as a function of ten parameters: eight effective rate constants, and NT$\sb3$ and NT$\sb4$. We tested the model in four sets of published experimental data, by identifying the effective rate constants plus NT$\sb3$ and NT$\sb4$. The model was found to fit the data well, and the values of the parameters were apparently consistent with smooth muscle physiology, or plausible explanations could be postulated for their values. The ATP turnover energetic predictions of the model were off the experimental values by a factor of fifty, in one set where this test could be done. We conclude that, although the model fits the data well, because of its energetic failure, it must be considered with strong reservations as a possible good representation of real smooth muscle. A possible reason for the failure of the model is that it is too simple. Considerations of the disparity in the number of crossbridges vs. myosin light chain kinase molecules, suggests that models that recognize this disparity would involve a large number of states. These models could have a higher ATP turnover than four state models, but at a cost of requiring much increased mathematical complexity for their quantitative analysis.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biophysics

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2011

Author dc:creator

• Lazalde, Carlos Armando

Contributors dc:contributor

• Barr, L.

• Biology, Animal Physiology
• Chemistry, Biochemistry
• Biophysics, General

Statement dc:rights

• Copyright 1992 Lazalde, Carlos Armando

Language dc:language

eng

Identifier

AAI9236513
(UMI)AAI9236513

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/23309