Niederer, Smith, 2007

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.