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Titolo:
Ca2+ activation of myofilaments from transgenic mouse hearts expressing R92Q mutant cardiac troponin T
Autore:
Chandra, M; Rundell, VLM; Tardiff, JC; Leinwand, LA; De Tombe, PP; Solaro, RJ;
Indirizzi:
Univ Illinois, Coll Med, Dept Physiol & Biophys MC 901, Chicago, IL 60612 USA Univ Illinois Chicago IL USA 60612 Biophys MC 901, Chicago, IL 60612 USA Univ Illinois, Coll Med, Cardiovasc Sci Program, Chicago, IL 60612 USA Univ Illinois Chicago IL USA 60612 asc Sci Program, Chicago, IL 60612 USA Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA Albert Einstein Coll Med Bronx NY USA 10461 Dept Med, Bronx, NY 10461 USA Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA Univ Colorado Boulder CO USA 80309 ular & Dev Biol, Boulder, CO 80309 USA
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
fascicolo: 2, volume: 280, anno: 2001,
pagine: H705 - H713
SICI:
0363-6135(200102)280:2<H705:CAOMFT>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; MYOFIBRILLAR ATPASE ACTIVITY; SKINNED MUSCLE-FIBERS; THIN-FILAMENT; SKELETAL-MUSCLE; TENSION DEVELOPMENT; SARCOMERE-LENGTH; FORCE PRODUCTION; RAT; TROPOMYOSIN;
Keywords:
skinned fiber bundles; contraction; calcium sensitivity; crossbridge cycling; rate constant of tension redevelopment;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Chandra, M Univ Illinois, Coll Med, Dept Physiol & Biophys MC 901, 835 S Wolcott Ave,Chicago, IL 60612 USA Univ Illinois 835 S Wolcott Ave Chicago ILUSA 60612 60612 USA
Citazione:
M. Chandra et al., "Ca2+ activation of myofilaments from transgenic mouse hearts expressing R92Q mutant cardiac troponin T", AM J P-HEAR, 280(2), 2001, pp. H705-H713

Abstract

The functional consequences of the R92Q mutation in cardiac troponin T (cTnT), linked to familial hypertrophic cardiomyopathy in humans, are not wellunderstood. We have studied steady- and pre-steady-state mechanical activity of detergent-skinned fiber bundles from a transgenic (TG) mouse model inwhich 67% of the total cTnT in the heart was replaced by the R92Q mutant cTnT. TG fibers were more sensitive to Ca2+ than nontransgenic (NTG) fibers [negative logarithm of half maximally activating molar Ca2+ (pCa(50)) = 5.84 +/- 0.01 and 6.12 +/- 0.01 for NTG and TG fibers, respectively]. The shift in pCa50 caused by increasing the sarcomere length from 1.9 to 2.3 mum was significantly higher for TG than for NTG fibers (Delta pCa(50) = 0.13 +/-0.01 and 0.29 +/- 0.02 for NTG and TG fibers, respectively). The relationships between rate of ATP consumption and steady- state isometric tension were linear, and the slopes were the same in NTG and TG fibers. Rate of tension redevelopment was more sensitive to Ca2+ in TG than in NTG fibers (pCa(50) = 5.71 +/- 0.02 and 6.07 +/- 0.02 for NTG and TG fibers, respectively). We concluded that overall cross-bridge cycling kinetics are not altered by the R92Q mutation but that altered troponin-tropomyosin interactions could be responsible for the increase in myofilament Ca2+ sensitivity in TG myofilaments.

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Documento generato il 06/04/20 alle ore 08:27:35