A Mathematical Model of the Slow Force Response to Stretch in Rat Ventricular Myocytes

Model Status

This model is known to run in both OpenCell and COR to reproduce the output shown in the publication.

Model Structure

ABSTRACT: We developed a model of the rat ventricular myocyte at room temperature to predict the relative effects of different mechanisms on the cause of the slow increase in force in response to a step change in muscle length. We performed simulations in the presence of stretch-dependent increases in flux through the Na+-H+ exchanger (NHE) and chloride-bicarbonate exchanger (AE), stretch-activated channels (SAC), and the stretch-dependent nitric oxide (NO) induced increased open probability of the ryanodine receptors to estimate the capacity of each mechanism to produce the slow force response (SFR). Inclusion of stretch-dependent NHE & AE, SACs, and stretch-dependent NO effects caused an increase in tension following 15 min of stretch of 0.87%, 32%, and 0%, respectively. Comparing [Ca2+]i dynamics before and after stretch in the presence of combinations of the three stretch-dependent elements, which produced significant SFR values (>20%), showed that the inclusion of stretch-dependent NO effects produced [Ca2+]i transients, which were not consistent with experimental results. Further simulations showed that in the presence of SACs and the absence of stretch-dependent NHE & AE inhibition of NHE attenuated the SFR, such that reduced SFR in the presence of NHE blockers does not indicate a stretch dependence of NHE. Rather, a functioning NHE is responsible for a portion of the SFR. Based on our simulations we estimate that in rat cardiac myocytes at room temperature SACs play a significant role in producing the SFR, potentially in the presence of stretch-dependent NHE & AE and that NO effects, if any, must involve more mechanisms than just increasing the open probability of ryanodine receptors.

The complete original publication reference is cited below:

A mathematical model of the slow force response to stretch in rat ventricular myocytes, Steven Niederer, Nicholas Smith, 2007. Biophysical Journal, 92 (11) 4030-4044, PubMed ID: 17369410

Schematic representation of the mathematical model.