This is an application for a renewal of a Program Project Grant, entitled, """"""""MOLECULAR MECHANISMS OF CONTRACTION"""""""". The projects are designed to elucidate the molecular processes by which critical systems in the heart regulate the intracellular calcium levels and thus, myocardial contractility. The information derived is fundamental towards the understanding of the factors involved in a dysfunctioning heart and will be valuable in the synthesis of new molecules that may prevent or reverse the disease processes. The six projects include studies on human heart voltage-dependent calcium channels, human Na, K-ATPase, myosin, troponin I, phospholamban in the sarcoplasmic reticulum, and a regulatory atrial apolipoprotein. All the projects are directed towards elucidating structure-function relationships and understanding regulatory mechanisms at the molecular level. All use molecular biological strategies and at least three are designed to extend their studies to an in vivo model and produce transgenic mice with specific characteristics. The scientific cores include molecular biology, protein chemistry and transgenic animal cardiovascular dynamics.
| Jagatheesan, Ganapathy; Rajan, Sudarsan; Wieczorek, David F (2010) Investigations into tropomyosin function using mouse models. J Mol Cell Cardiol 48:893-8 |
| Fuller-Bicer, Geraldine A; Varadi, Gyula; Koch, Sheryl E et al. (2009) Targeted disruption of the voltage-dependent calcium channel alpha2/delta-1-subunit. Am J Physiol Heart Circ Physiol 297:H117-24 |
| Sadayappan, Sakthivel; Finley, Natosha; Howarth, Jack W et al. (2008) Role of the acidic N'region of cardiac troponin I in regulating myocardial function. FASEB J 22:1246-57 |
| Pattison, James Scott; Waggoner, Jason R; James, Jeanne et al. (2008) Phospholamban overexpression in transgenic rabbits. Transgenic Res 17:157-70 |
| Jagatheesan, Ganapathy; Rajan, Sudarsan; Petrashevskaya, Natalia et al. (2007) Rescue of tropomyosin-induced familial hypertrophic cardiomyopathy mice by transgenesis. Am J Physiol Heart Circ Physiol 293:H949-58 |
| Scragg, Jason L; Fearon, Ian M; Boyle, John P et al. (2005) Alzheimer's amyloid peptides mediate hypoxic up-regulation of L-type Ca2+ channels. FASEB J 19:150-2 |
| Rubio, Marta; Bodi, Ilona; Fuller-Bicer, Geraldine A et al. (2005) Sarcoplasmic reticulum adenosine triphosphatase overexpression in the L-type Ca2+ channel mouse results in cardiomyopathy and Ca2+ -induced arrhythmogenesis. J Cardiovasc Pharmacol Ther 10:235-49 |
| Bodi, Ilona; Mikala, Gabor; Koch, Sheryl E et al. (2005) The L-type calcium channel in the heart: the beat goes on. J Clin Invest 115:3306-17 |
| Petrashevskaya, Natalia N; Bodi, Ilona; Koch, Sheryl E et al. (2004) Effects of alpha1-adrenergic stimulation on normal and hypertrophied mouse hearts. Relation to caveolin-3 expression. Cardiovasc Res 63:561-72 |
| Groner, Ferdi; Rubio, Marta; Schulte-Euler, Patrick et al. (2004) Single-channel gating and regulation of human L-type calcium channels in cardiomyocytes of transgenic mice. Biochem Biophys Res Commun 314:878-84 |
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