Abstract

The project is designed to increase our knowledge of the excitation-contraction coupling process in the mammalian heart. The focus is to define the characteristics of calcium (Ca) at the myocardial sarcolemma, including definition of binding sites, factors important in the determination of the quantity bound, relation of bound Ca to transsarcolemmal movement and subsequent cellular distribution and the relation of this Ca to the process of contractile control. Methodology will include (1) zeta potential measurement in vesicles and single cells, (2) vesicle aggregation studies, (3) 45Ca exchange measurement in single cells with """"""""scintillation sieve"""""""" technique, (4) measurement of contraction amplitude of single cells by video technique under conditions of rapid perfusion, (5) ionic current measurement with single cell voltage clamp, (6) ionic compartmentation analysis with electron microprobe, (7) membrane ultrastructure with electron microscopy and freeze-fracture technique and (8) measurement of excitation-dependent Ca uptake and function in intact, arterially-perfused ventricular tissue. The project is designed to be comprehensive in that Ca binding characteristics at the molecular level will be correlated with cellular exchange and contractile function. Knowledge gained from this project can be related to contractile control of the heart in situ, as a foundation for comparison of ionic events following cardiac ischemia and reperfusion and to increase understanding of the action of drugs on cardiac function in the clinical situation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL028539-07
Application #
3339910
Study Section
Cardiovascular Study Section (CVA)
Project Start
1982-05-01
Project End
1992-04-30
Budget Start
1988-05-01
Budget End
1989-04-30
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Ponce-Hornos, J E; Philipson, K D; Bonazzola, P et al. (1999) Energetics of Na(+)-Ca(2+) exchange in resting cardiac muscle. Biophys J 77:3319-27
Marengo, F D; Wang, S Y; Wang, B et al. (1998) Dependence of cardiac cell Ca2+ permeability on sialic acid-containing sarcolemmal gangliosides. J Mol Cell Cardiol 30:127-37
Korge, P; Langer, G A (1998) Mitochondrial Ca2+ uptake, efflux, and sarcolemmal damage in Ca2+-overloaded cultured rat cardiomyocytes. Am J Physiol 274:H2085-93
Marengo, F D; Wang, S Y; Langer, G A (1997) The effects of temperature upon calcium exchange in intact cultured cardiac myocytes. Cell Calcium 21:263-73
Langer, G A; Peskoff, A (1997) Role of the diadic cleft in myocardial contractile control. Circulation 96:3761-5
Barrigon, S; Wang, S Y; Ji, X et al. (1996) Characterization of the calcium overload in cultured neonatal rat cardiomyocytes under metabolic inhibition. J Mol Cell Cardiol 28:1329-37
Wang, S Y; Peskoff, A; Langer, G A (1996) Inner sarcolemmal leaflet Ca(2+) binding: its role in cardiac Na/Ca exchange. Biophys J 70:2266-74
Wang, S Y; Clague, J R; Langer, G A (1995) Increase in calcium leak channel activity by metabolic inhibition or hydrogen peroxide in rat ventricular myocytes and its inhibition by polycation. J Mol Cell Cardiol 27:211-22
Clague, J R; Langer, G A (1994) The pathogenesis of free radical-induced calcium leak in cultured rat cardiomyocytes. J Mol Cell Cardiol 26:11-21
Ji, S; Weiss, J N; Langer, G A (1993) Modulation of voltage-dependent sodium and potassium currents by charged amphiphiles in cardiac ventricular myocytes. Effects via modification of surface potential. J Gen Physiol 101:355-75

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