title: NH2-terminal truncations of cardiac troponin I and cardiac troponin T produce distinct effects on contractility and calcium homeostasis in adult cardiomyocytes.
abstract: Cardiac troponin I (TnI) has an NH2-terminal extension that is an adult heart-specific regulatory structure. Restrictive proteolytic truncation of the NH2-terminal extension of cardiac TnI occurs in normal hearts and is upregulated in cardiac adaptation to hemodynamic stress or β-adrenergic deficiency. NH2-terminal truncated cardiac TnI (cTnI-ND) alters the conformation of the core structure of cardiac TnI similarly to that produced by PKA phosphorylation of Ser(23/24) in the NH2-terminal extension. At organ level, cTnI-ND enhances ventricular diastolic function. The NH2-terminal region of cardiac troponin T (TnT) is another regulatory structure that can be selectively cleaved via restrictive proteolysis. Structural variations in the NH2-terminal region of TnT also alter the molecular conformation and function. Transgenic mouse hearts expressing NH2-terminal truncated cardiac TnT (cTnT-ND) showed slower contractile velocity to prolong ventricular rapid-ejection time, resulting in higher stroke volume. Our present study compared the effects of cTnI-ND and cTnT-ND in cardiomyocytes isolated from transgenic mice on cellular morphology, contractility, and calcium kinetics. Resting cTnI-ND, but not cTnT-ND, cardiomyocytes had shorter length than wild-type cells with no change in sarcomere length. cTnI-ND, but not cTnT-ND, cardiomyocytes produced higher contractile amplitude and faster shortening and relengthening velocities in the absence of external load than wild-type controls. Although the baseline and peak levels of cytosolic Ca(2+) were not changed, Ca(2+) resequestration was faster in both cTnI-ND and cTnT-ND cardiomyocytes than in wild-type control. The distinct effects of cTnI-ND and cTnT-ND demonstrate their roles in selectively modulating diastolic or systolic functions of the heart.
authors.affiliation: Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Hongguang
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan jjin@med.wayne.edu.
authors.forename: J-P
authors.initials: JP
authors.lastname: Jin
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000502:physiology*; D019210:Troponin I / Q000096:biosynthesis* / Q000235:genetics; D020107:Troponin T / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D019210:Troponin I; D020107:Troponin T; D002118:Calcium
keywords: cardiac troponin I; cardiac troponin T; contractility; intracellular calcium transient; isolated mouse adult cardiomyocyte