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Length dependence of striated muscle force generation is controlled by phosphorylation of cTnI at serines 23/24


Journal of Physiology 591(18): 4535-4547
Length dependence of striated muscle force generation is controlled by phosphorylation of cTnI at serines 23/24
According to the Frank-Starling relationship, greater end diastolic volume increases ventricular output. The Frank-Starling relationship is based, in part, on the length-tension relationship in cardiac myocytes. Recently, we identified a dichotomy in the steepness of length-tension relationships in mammalian cardiac myocytes that was dependent upon PKA-induced myofibrillar phosphorylation. Since PKA has multiple myofibrillar substrates including titin, myosin binding protein-C (MyBP-C), and cardiac troponin I (cTnI), we sought to define if phosphorylation of one of these molecules could control length-tension relationships. We focused on cTnI since troponin can be exchanged in permeabilized striated muscle cell preparations and tested the hypothesis that phosphorylation of cTnI modulates length dependence of force generation. For these experiments, we exchanged unphosphorylated recombinant cardiac troponin (cTn) into either a rat cardiac myocyte preparation or a skinned slow-twitch skeletal muscle fibre. In all cases unphosphorylated cTn yielded a shallow length-tension relationship, which was shifted to a steep relationship after PKA treatment. Furthermore, exchange with cTn having cTnI serines 23 and 24 mutated to aspartic acids to mimic phosphorylation always shifted a shallow length-tension relationship to a steep relationship. Overall, these results indicate that phosphorylation of cTnI serines 23/24 is a key regulator of length dependence of force generation in striated muscle.This article is protected by copyright. All rights reserved.


Accession: 036967585

PMID: 23836688

DOI: 10.1113/jphysiol.2013.258400



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