- Author:
- aram148 <42922407+aram148@users.noreply.github.com>
- Date:
- 2022-07-22 15:47:05+12:00
- Desc:
- Added documentation for VSM model
- Permanent Source URI:
- https://models.fieldml.org/workspace/6b0/rawfile/a8a92308e217ac5626809237dd90a31240b22834/USMC/hai1.cellml
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<!-- var kappa: dimensionless {pub: in};-->
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vars k1 and k1;-->
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<title xmlns="http://cellml.org/tmp-documentation">Cross-bridge phosphorylation and regulation of latch state in smooth muscle</title>
<author xmlns="http://cellml.org/tmp-documentation">
<firstname xmlns="http://cellml.org/tmp-documentation">Catherine</firstname>
<surname xmlns="http://cellml.org/tmp-documentation">Lloyd</surname>
<affiliation xmlns="http://cellml.org/tmp-documentation">
<shortaffil xmlns="http://cellml.org/tmp-documentation">Auckland Bioengineering Institute, The University of Auckland</shortaffil>
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<section xmlns="http://cellml.org/tmp-documentation" id="sec_status">
<title xmlns="http://cellml.org/tmp-documentation">Model Status</title>
<para xmlns="http://cellml.org/tmp-documentation">
This CellML model runs in both OpenCell and COR to replicate the published results (figure 6a). The units have been checked and they are consistent.
</para>
</section>
<sect1 xmlns="http://cellml.org/tmp-documentation" id="sec_structure">
<title xmlns="http://cellml.org/tmp-documentation">Model Structure</title>
<para xmlns="http://cellml.org/tmp-documentation">
ABSTRACT: We have developed a minimum kinetic model for cross-bridge interactions with the thin filament in smooth muscle. The model hypothesizes two types of cross-bridge interactions: 1) cycling phosphorylated cross bridges and 2) noncycling dephosphorylated cross bridges ("latch bridges"). The major assumptions are that 1) Ca2+-dependent myosin phosphorylation is the only postulated regulatory mechanism, 2) each myosin head acts independently, and 3) latch bridges are formed by dephosphorylation of an attached cross bridge. Rate constants were resolved by fitting data on the time courses of myosin phosphorylation and stress development. Comparison of the rate constants indicates that latch-bridge detachment is the rate-limiting step. Model simulations predicted a hyperbolic dependence of steady-state stress on myosin phosphorylation, which corresponded with the experimental observation of high values of stress with low levels of phosphorylation in intact tissues. Model simulations also predicted the experimental observation that an initial phosphorylation transient only accelerates stress development, with no effect on the final steady-state levels of stress. Because the only Ca2+-dependent regulatory mechanism in this model was activation of myosin light chain kinase, these results are consistent with the hypothesis that myosin phosphorylation is both necessary and sufficient for the development of the latch state.
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<para xmlns="http://cellml.org/tmp-documentation">
The original paper reference is cited below:
</para>
<para xmlns="http://cellml.org/tmp-documentation">
Cross-bridge phosphorylation and regulation of latch state in smooth muscle, Hai CM, Murphy RA, 1988, <emphasis xmlns="http://cellml.org/tmp-documentation">American Journal of Physiology</emphasis>, 254, C99-C106. <ulink xmlns="http://cellml.org/tmp-documentation" url="http://www.ncbi.nlm.nih.gov/pubmed/3337223">PubMed ID: 3337223</ulink>
</para>
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<title xmlns="http://cellml.org/tmp-documentation">reaction diagram</title>
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<imagedata xmlns="http://cellml.org/tmp-documentation" fileref="hai_1988.png"/>
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<caption xmlns="http://cellml.org/tmp-documentation">Hai and Murphy's four-state model: the latch regulatory scheme for Ca<superscript xmlns="http://cellml.org/tmp-documentation">2+</superscript>-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.</caption>
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</sect1>
</article>
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<dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">
Cross-bridge phosphorylation and regulation of latch state in smooth muscle
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