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• W1966871724 startingPage "177" @default.
• W1966871724 abstract "The binding of Ca(2+) to troponin C (TnC) in the troponin complex is a critical step regulating the thin filament, the actin-myosin interaction and cardiac contraction. Phosphorylation of the troponin complex is a key regulatory mechanism to match cardiac contraction to demand. Here we demonstrate that phosphorylation of the troponin I (TnI) subunit is simultaneously increased at Ser-150 and Ser-23/24 during in vivo myocardial ischemia. Myocardial ischemia decreases intracellular pH resulting in depressed binding of Ca(2+) to TnC and impaired contraction. To determine the pathological relevance of these simultaneous TnI phosphorylations we measured individual TnI Ser-150 (S150D), Ser-23/24 (S23/24D) and combined (S23/24/150D) pseudo-phosphorylation effects on thin filament regulation at acidic pH similar to that in myocardial ischemia. Results demonstrate that while acidic pH decreased thin filament Ca(2+) binding to TnC regardless of TnI composition, TnI S150D attenuated this decrease rendering it similar to non-phosphorylated TnI at normal pH. The dissociation of Ca(2+) from TnC was unaltered by pH such that TnI S150D remained slow, S23/24D remained accelerated and the combined S23/24/150D remained accelerated. This effect of the combined TnI Ser-150 and Ser-23/24 pseudo-phosphorylations to maintain Ca(2+) binding while accelerating Ca(2+) dissociation represents the first post-translational modification of troponin by phosphorylation to both accelerate thin filament deactivation and maintain Ca(2+) sensitive activation. These data suggest that TnI Ser-150 phosphorylation induced attenuation of the pH-dependent decrease in Ca(2+) sensitivity and its combination with Ser-23/24 phosphorylation to maintain accelerated thin filament deactivation may impart an adaptive role to preserve contraction during acidic ischemia pH without slowing relaxation." @default.
• W1966871724 created "2016-06-24" @default.
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• W1966871724 date "2014-07-01" @default.
• W1966871724 modified "2023-09-27" @default.
• W1966871724 title "Combined troponin I Ser-150 and Ser-23/24 phosphorylation sustains thin filament Ca2+ sensitivity and accelerates deactivation in an acidic environment" @default.
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• W1966871724 doi "https://doi.org/10.1016/j.yjmcc.2014.03.010" @default.
• W1966871724 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4075059" @default.
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