The overall goal of this project is to determine the factors which govern the efficiency of the sarcoplasmic reticulum in the coupling of ATP utilization to the regulation of intracellular Ca2 ion levels in cardiac muscle. These studies proposed here center initially on a determination of the dynamical structure at the submolecular level of the sarcoplasmic reticulum membrane and its functionally relevant model membranes as determined primarily by X-ray and neutron diffraction. The dynamical structure of the natural and model membranes will be studied """"""""at rest"""""""" and during the time-course of Ca2 ion uptake and Ca2 ion release. Through such studies and a correlation of systematic structural and dynamical modification of the membranes with their resulting perturbed energy-coupling efficiencies, we hope to gain insight into the molecular mechanism of Ca2 ion transport and the structural and dynamical factors which govern the degree of energy coupling in this regulatory membrane.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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University of Pennsylvania
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Cefaratti, C; Romani, A (2011) Modulation of Na+/Mg²+ exchanger stoichiometry ratio by Cl? ions in basolateral rat liver plasma membrane vesicles. Mol Cell Biochem 351:133-42
Prosdocimo, Domenick A; Wyler, Steven C; Romani, Andrea M et al. (2010) Regulation of vascular smooth muscle cell calcification by extracellular pyrophosphate homeostasis: synergistic modulation by cyclic AMP and hyperphosphatemia. Am J Physiol Cell Physiol 298:C702-13
Dubyak, George R (2009) Both sides now: multiple interactions of ATP with pannexin-1 hemichannels. Focus on ""A permeant regulating its permeation pore: inhibition of pannexin 1 channels by ATP"". Am J Physiol Cell Physiol 296:C235-41
Prosdocimo, Domenick A; Douglas, Dezmond C; Romani, Andrea M et al. (2009) Autocrine ATP release coupled to extracellular pyrophosphate accumulation in vascular smooth muscle cells. Am J Physiol Cell Physiol 296:C828-39
Kasturi, Sriram; Ismail-Beigi, Faramarz (2008) Effect of thyroid hormone on the distribution and activity of Na, K-ATPase in ventricular myocardium. Arch Biochem Biophys 475:121-7
Blum, Andrew E; Joseph, Sheldon M; Przybylski, Ronald J et al. (2008) Rho-family GTPases modulate Ca(2+) -dependent ATP release from astrocytes. Am J Physiol Cell Physiol 295:C231-41
Ballard, Brandon; Torres, Lisa M; Romani, Andrea (2008) Effect of thyroid hormone on Mg(2+) homeostasis and extrusion in cardiac cells. Mol Cell Biochem 318:117-27
Marengo, Susan R; Romani, Andrea M P (2008) Oxalate in renal stone disease: the terminal metabolite that just won't go away. Nat Clin Pract Nephrol 4:368-77
Reed, Grant; Cefaratti, Christie; Berti-Mattera, Liliana N et al. (2008) Lack of insulin impairs Mg2+ homeostasis and transport in cardiac cells of streptozotocin-injected diabetic rats. J Cell Biochem 104:1034-53
Cefaratti, Christie; Romani, Andrea M P (2007) Functional characterization of two distinct Mg(2+) extrusion mechanisms in cardiac sarcolemmal vesicles. Mol Cell Biochem 303:63-72

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