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• W2255365909 abstract "Calcium-induced calcium release is the principal mechanism that triggers the cell-wide [Ca2+]i transient that activates muscle contraction during cardiac excitation-contraction coupling (ECC). Here, we characterize this process in mouse cardiac myocytes with a novel mathematical action potential (AP) model that incorporates realistic stochastic gating of voltage-dependent L-type calcium (Ca2+) channels (LCCs) and sarcoplasmic reticulum (SR) Ca2+ release channels (the ryanodine receptors, RyR2s). Depolarization of the sarcolemma during an AP stochastically activates the LCCs elevating subspace [Ca2+] within each of the cell's 20,000 independent calcium release units (CRUs) to trigger local RyR2 opening and initiate Ca2+ sparks, the fundamental unit of triggered Ca2+ release. Synchronization of Ca2+ sparks during systole depends on the nearly uniform cellular activation of LCCs and the likelihood of local LCC openings triggering local Ca2+ sparks (ECC fidelity). The detailed design and true SR Ca2+ pump/leak balance displayed by our model permits investigation of ECC fidelity and Ca2+ spark fidelity, the balance between visible (Ca2+ spark) and invisible (Ca2+ quark/sub-spark) SR Ca2+ release events. Excess SR Ca2+ leak is examined as a disease mechanism in the context of “catecholaminergic polymorphic ventricular tachycardia (CPVT)”, a Ca2+-dependent arrhythmia. We find that that RyR2s (and therefore Ca2+ sparks) are relatively insensitive to LCC openings across a wide range of membrane potentials; and that key differences exist between Ca2+ sparks evoked during quiescence, diastole, and systole. The enhanced RyR2 [Ca2+]i sensitivity during CPVT leads to increased Ca2+ spark fidelity resulting in asynchronous systolic Ca2+ spark activity. It also produces increased diastolic SR Ca2+ leak with some prolonged Ca2+ sparks that at times become “metastable” and fail to efficiently terminate. There is a huge margin of safety for stable Ca2+ handling within the cell and this novel mechanistic model provides insight into the molecular signaling characteristics that help maintain overall Ca2+ stability even under the conditions of high SR Ca2+ leak during CPVT. Finally, this model should provide tools for investigators to examine normal and pathological Ca2+ signaling characteristics in the heart." @default.
• W2255365909 created "2016-06-24" @default.
• W2255365909 creator A5042893358 @default.
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• W2255365909 date "2016-03-01" @default.
• W2255365909 modified "2023-09-29" @default.
• W2255365909 title "Ryanodine receptor sensitivity governs the stability and synchrony of local calcium release during cardiac excitation-contraction coupling" @default.
• W2255365909 cites W1502527850 @default.
• W2255365909 cites W1567439183 @default.
• W2255365909 cites W1823244892 @default.
• W2255365909 cites W1899233195 @default.
• W2255365909 cites W1963643075 @default.
• W2255365909 cites W1965371036 @default.
• W2255365909 cites W1972183015 @default.
• W2255365909 cites W1974668957 @default.
• W2255365909 cites W1977643020 @default.
• W2255365909 cites W1982140992 @default.
• W2255365909 cites W1983381233 @default.
• W2255365909 cites W1983707293 @default.
• W2255365909 cites W1985749037 @default.
• W2255365909 cites W1986783128 @default.
• W2255365909 cites W1988172324 @default.
• W2255365909 cites W1988382203 @default.
• W2255365909 cites W1990406674 @default.
• W2255365909 cites W1993347480 @default.
• W2255365909 cites W1993880054 @default.
• W2255365909 cites W1994147843 @default.
• W2255365909 cites W1995005951 @default.
• W2255365909 cites W1999797985 @default.
• W2255365909 cites W2005865511 @default.
• W2255365909 cites W2008864455 @default.
• W2255365909 cites W2011038097 @default.
• W2255365909 cites W2017378812 @default.
• W2255365909 cites W2020183500 @default.
• W2255365909 cites W2021622307 @default.
• W2255365909 cites W2035438595 @default.
• W2255365909 cites W2036874203 @default.
• W2255365909 cites W2037899064 @default.
• W2255365909 cites W2042646075 @default.
• W2255365909 cites W2046175896 @default.
• W2255365909 cites W2046526051 @default.
• W2255365909 cites W2050553914 @default.
• W2255365909 cites W2059424963 @default.
• W2255365909 cites W2059784324 @default.
• W2255365909 cites W2062157267 @default.
• W2255365909 cites W2065076724 @default.
• W2255365909 cites W2076273945 @default.
• W2255365909 cites W2076698517 @default.
• W2255365909 cites W2080484314 @default.
• W2255365909 cites W2087116178 @default.
• W2255365909 cites W2088794766 @default.
• W2255365909 cites W2090116945 @default.
• W2255365909 cites W2097697208 @default.
• W2255365909 cites W2098044063 @default.
• W2255365909 cites W2099869024 @default.
• W2255365909 cites W2102924449 @default.
• W2255365909 cites W2107191374 @default.
• W2255365909 cites W2111394029 @default.
• W2255365909 cites W2111827793 @default.
• W2255365909 cites W2118098701 @default.
• W2255365909 cites W2124672573 @default.
• W2255365909 cites W2125849261 @default.
• W2255365909 cites W2127926880 @default.
• W2255365909 cites W2129115366 @default.
• W2255365909 cites W2131750503 @default.
• W2255365909 cites W2132561989 @default.
• W2255365909 cites W2134064208 @default.
• W2255365909 cites W2135771733 @default.
• W2255365909 cites W2139133121 @default.
• W2255365909 cites W2143078236 @default.
• W2255365909 cites W2143934697 @default.
• W2255365909 cites W2146036536 @default.
• W2255365909 cites W2147334907 @default.
• W2255365909 cites W2149826121 @default.
• W2255365909 cites W2151989861 @default.
• W2255365909 cites W2153888863 @default.
• W2255365909 cites W2326180962 @default.
• W2255365909 cites W2531345437 @default.
• W2255365909 cites W2995745386 @default.
• W2255365909 cites W4239219601 @default.
• W2255365909 doi "https://doi.org/10.1016/j.yjmcc.2016.01.024" @default.
• W2255365909 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4807626" @default.
• W2255365909 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26827896" @default.
• W2255365909 hasPublicationYear "2016" @default.
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