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Titolo:
SKELETAL TROPONIN-C REDUCES CONTRACTILE SENSITIVITY TO ACIDOSIS IN CARDIAC MYOCYTES FROM TRANSGENIC MICE
Autore:
METZGER JM; PARMACEK MS; BARR E; PASYK K; LIN WI; COCHRANE KL; FIELD LJ; LEIDEN JM;
Indirizzi:
UNIV MICHIGAN,SCH MED,DEPT PHYSIOL,7730 MED SCI II ANN ARBOR MI 48109 UNIV CHICAGO,DEPT MED CHICAGO IL 60637 INDIANA UNIV,SCH MED,KRANNERT INST CARDIOL INDIANAPOLIS IN 46202
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 19, volume: 90, anno: 1993,
pagine: 9036 - 9040
SICI:
0027-8424(1993)90:19<9036:STRCST>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
THIN FILAMENT ACTIVATION; MUSCLE FIBERS; RAT-HEART; PH; FORCE; TRANSITION; EXTRACTION; ISCHEMIA; TENSION; CA-2+;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
25
Recensione:
Indirizzi per estratti:
Citazione:
J.M. Metzger et al., "SKELETAL TROPONIN-C REDUCES CONTRACTILE SENSITIVITY TO ACIDOSIS IN CARDIAC MYOCYTES FROM TRANSGENIC MICE", Proceedings of the National Academy of Sciences of the United Statesof America, 90(19), 1993, pp. 9036-9040

Abstract

Depressed contractile function plays a primary role in the pathophysiology of acute myocardial ischemia. Intracellular acidification is an important factor underlying the inhibition of force production in the ischemic myocardium. The effect of acidosis to depress contractility is markedly greater in cardiac as compared to skeletal muscle; however,the molecular basis of this difference in sensitivity to acidosis is not dearly understood. In this report, we describe transgenic mice that express the fast skeletal isoform of troponin C (sTnC) in cardiac muscle. In permeabilized single cardiac myocytes the shift in the midpoint of the tension-pCa relationship (i.e., pCa50, where pCa is -log[Ca2]) due to lowering pH from 7.00 to 6.20 was 1.27 +/- 0.03 (n = 7) pCaunits in control cardiac TnC (cTnC) expressing myocytes and 0.96 +/- 0.04 (n = 11) pCa unit in transgenic cardiac myocytes (P < 0.001). Theeffect of pH to alter maximum Ca2+-activated tension was unchanged byTnC isoforms in these cardiac myocytes. In a reciprocal experiment, contractile sensitivity to acidosis was increased in fast skeletal muscle fibers following extraction of endogenous sTnC and reconstitution with purified cTnC in vitro. Our findings demonstrate that TnC plays animportant role in determining the profound sensitivity of cardiac muscle to acidosis and identify cTnC as a target for therapeutic interventions designed to modify ischemia-induced myocardial contractile dysfunction.

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Documento generato il 26/09/20 alle ore 08:39:16