期刊
BIOPHYSICAL JOURNAL
卷 87, 期 6, 页码 3723-3736出版社
BIOPHYSICAL SOCIETY
DOI: 10.1529/biophysj.104.049973
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资金
- NHLBI NIH HHS [R01 HL061711, R01 HL-60133, R01 HL072488, R01 HL060133, R01 HL-72488, R01 HL-61711, N01 HV028180, P50 HL-52307] Funding Source: Medline
Calcium (Ca2+)-induced Ca2+ release (CICR) in cardiac myocytes exhibits high gain and is graded. These properties result from local control of Ca2+ release. Existing local control models of Ca2+ release in which interactions between L-Type Ca2+ channels (LCCs) and ryanodine-sensitive Ca2+ release channels (RyRs) are simulated stochastically are able to reconstruct these properties, but only at high computational cost. Here we present a general analytical approach for deriving simplified models of local control of CICR, consisting of low-dimensional systems of coupled ordinary differential equations, from these more complex local control models in which LCC-RyR interactions are simulated stochastically. The resulting model, referred to as the coupled LCC-RyR gating model, successfully reproduces a range of experimental data, including L-Type Ca2+ current in response to voltage-clamp stimuli, inactivation of LCC current with and without Ca2+ release from the sarcoplasmic reticulum, voltage-dependence of excitation-contraction coupling gain, graded release, and the force-frequency relationship. The model does so with low computational cost.
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