Abstract

description): This proposal studies calcium regulation in intact ventricular cells with a focus on sarcoplasmic reticulum (SR) calcium release and the sodium/calcium (Na/Ca) exchanger. The proposal has three specific aims.
Specific aim 1 determines the amount of calcium released during a calcium spark and the number of SR calcium release channels (ryanodine receptors, RYRs) contributing to a calcium spark (i.e. cluster size).
Specific aim 2 measures the flux of SR calcium release during an action potential.
Specific aim 3 explores the contribution of Na/Ca exchange current to the action potential and the trigger for SR calcium release. The majority of these studies will be performed on single cardiac ventricular cells isolated from adult rabbits, rats, mice and ferrets. Membrane currents (both whole cell and single channel) will be measured with the patch clamp technique. Whole-cell calcium transients will be measured with indo-1 by standard techniques in epifluorescence microscopy. Local calcium transients (calcium sparks and sarcolemmal calcium transients) will be visualized as fluo-3 fluorescence with laser scanning confocal microscopy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL064098-04
Application #
6627545
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Program Officer
Reinlib, Leslie
Project Start
2000-01-15
Project End
2004-12-31
Budget Start
2003-01-01
Budget End
2003-12-31
Support Year
4
Fiscal Year
2003
Total Cost
$392,037
Indirect Cost

  Institution

Name
Loyola University Chicago
Department
Physiology
Type
Schools of Medicine
DUNS #
791277940
City
Maywood
State
IL
Country
United States
Zip Code
60153

  Publications

DeSantiago, J; Maier, L S; Bers, D M (2004) Phospholamban is required for CaMKII-dependent recovery of Ca transients and SR Ca reuptake during acidosis in cardiac myocytes. J Mol Cell Cardiol 36:67-74
Bassani, Rosana A; Altamirano, Julio; Puglisi, Jose L et al. (2004) Action potential duration determines sarcoplasmic reticulum Ca2+ reloading in mammalian ventricular myocytes. J Physiol 559:593-609
Bers, Donald M (2004) Macromolecular complexes regulating cardiac ryanodine receptor function. J Mol Cell Cardiol 37:417-29
Shannon, Thomas R; Wang, Fei; Puglisi, Jose et al. (2004) A mathematical treatment of integrated Ca dynamics within the ventricular myocyte. Biophys J 87:3351-71
Ginsburg, Kenneth S; Bers, Donald M (2004) Modulation of excitation-contraction coupling by isoproterenol in cardiomyocytes with controlled SR Ca2+ load and Ca2+ current trigger. J Physiol 556:463-80
Despa, Sanda; Kockskamper, Jens; Blatter, Lothar A et al. (2004) Na/K pump-induced [Na](i) gradients in rat ventricular myocytes measured with two-photon microscopy. Biophys J 87:1360-8
Ziolo, Mark T; Maier, Lars S; Piacentino 3rd, Valentino et al. (2004) Myocyte nitric oxide synthase 2 contributes to blunted beta-adrenergic response in failing human hearts by decreasing Ca2+ transients. Circulation 109:1886-91
Despa, S; Brette, F; Orchard, C H et al. (2003) Na/Ca exchange and Na/K-ATPase function are equally concentrated in transverse tubules of rat ventricular myocytes. Biophys J 85:3388-96
Piacentino 3rd, Valentino; Weber, Christopher R; Chen, Xiongwen et al. (2003) Cellular basis of abnormal calcium transients of failing human ventricular myocytes. Circ Res 92:651-8
Despa, Sanda; Bers, Donald M (2003) Na/K pump current and [Na](i) in rabbit ventricular myocytes: local [Na](i) depletion and Na buffering. Biophys J 84:4157-66

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