TnI Structural Interface with the N-Terminal Lobe of TnC as a Determinant of Cardiac Contractility.

ABSTRACT: The heterotrimeric cardiac troponin complex is a key regulator of contraction and plays an essential role in conferring Ca²⁺ sensitivity to the sarcomere. During ischemic injury, rapidly accumulating protons acidify the myoplasm, resulting in markedly reduced Ca²⁺ sensitivity of the sarcomere. Unlike the adult heart, sarcomeric Ca²⁺ sensitivity in fetal cardiac tissue is comparatively pH insensitive. Replacement of the adult cardiac troponin I (cTnI) isoform with the fetal troponin I (ssTnI) isoform renders adult cardiac contractile machinery relatively insensitive to acidification. Alignment and functional studies have determined histidine 132 of ssTnI to be the predominant source of this pH insensitivity. Substitution of histidine at the cognate position

SUBMITTER: Vetter AD 

PROVIDER: S-EPMC5954295 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature