Calcium sensitivity, force frequency relationship and cardiac troponin I: critical role of PKA and PKC phosphorylation sites.

ABSTRACT: Transgenic models with pseudo phosphorylation mutants of troponin I, PKA sites at Ser 22 and 23 (cTnIDD(22,23) mice) or PKC sites at Ser 42 and 44 (cTnIAD(22,23)DD(42,44)) displayed differential force-frequency relationships and afterload relaxation delay in vivo. We hypothesized that cTnI PKA and PKC phosphomimics impact cardiac muscle rate-related developed twitch force and relaxation kinetics in opposite directions. cTnIDD(22,23) transgenic mice produce a force frequency relationship (FFR) equivalent to control NTG albeit at lower peak [Ca(2+)](i), while cTnIAD(22,23)DD(42,44) TG mice had a flat FFR with normal peak systolic [Ca(2+)](i), thus suggestive of diminished responsiveness to [Ca(2+)](i) at higher frequencies. Force-[Ca(2+)](i) hysteresis analysis revealed that cTnIDD(22,23) mi

SUBMITTER: Ramirez-Correa GA 

PROVIDER: S-EPMC2854165 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature