"... In this study, we generalize a recently developed analytical
approach for deriving simplified mechanistic models of CICR
(Ca(2+)-induced Ca(2+) release) to formulate an integrative model of
the canine cardiac myocyte which is computationally efficient. The
resulting model faithfully reproduces experimentally measured
properties of EC (excitation-contraction) coupling and whole cell
phenomena. The model is used to study the role of local redundancy in
L-type Ca(2+) channel gating and the role of dyad configuration on EC
coupling. Simulations suggest that the characteristic steep rise in EC
coupling gain observed at hyperpolarized potentials is a result of
increased functional coupling between LCCs (L-type Ca(2+) channels)
and RyRs (ryanodine-sensitive Ca(2+) release channels). We also
demonstrate mechanisms by which alterations in the early
repolarization phase of the action potential, resulting from reduction
of the transient outward potassium current, alters properties of EC
coupling."
Reference:
1 .
Greenstein JL, Hinch R, Winslow RL (2006) Mechanisms of excitation-contraction coupling in an integrative model of the cardiac ventricular myocyte. Biophys J 90:77-91 [PubMed]
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