title: Cardiac troponin T mutations promote life-threatening arrhythmias.
abstract: Mutations in contractile proteins in heart muscle can cause anatomical changes that result in cardiac arrhythmias and sudden cardiac death. However, a conundrum has existed because mutations in one such contractile protein, a so-called Ca2+ sensor troponin T (TnT), can promote ventricular rhythm disturbances even in the absence of hypertrophy or fibrosis. Thus, these mutations must enhance abnormal electrophysiological events via alternative means. In this issue of the JCI, Baudenbacher et al. report a novel mechanism to explain this puzzle (see the related article beginning on page 3893). They show that a selected TnT mutation in the adult mouse heart can markedly increase the sensitivity of cardiac muscle myofilaments to Ca2+ and enhance the susceptibility to arrhythmia, even in the absence of anatomical deformities. As these same mutations can cause some forms of arrhythmias in humans, these findings are of both basic and translational significance.
authors.affiliation: Research Center, Montreal Heart Institute, Faculty of Pharmacy, University de Montréal, Montreal, Quebec, Canada.
authors.forename: Céline
authors.initials: C
authors.lastname: Fiset
authors.forename: Wayne R
authors.initials: WR
authors.lastname: Giles
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism* / Q000473:pathology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002312:Cardiomyopathy, Hypertrophic / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000009:adverse effects* / Q000494:pharmacology; D002415:Cats; D016757:Death, Sudden, Cardiac; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D005355:Fibrosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D011804:Quinolines / Q000009:adverse effects* / Q000494:pharmacology; D012307:Risk Factors; D017180:Tachycardia, Ventricular / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013829:Thiadiazines / Q000009:adverse effects* / Q000494:pharmacology; D020107:Troponin T / Q000235:genetics / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D006576:Heterocyclic Compounds, 4 or More Rings; D011804:Quinolines; D013829:Thiadiazines; D020107:Troponin T; C070609:EMD 53998; C472645:blebbistatin; D002118:Calcium