SR CA ATPASE, A DETERMINANT OF CARDIAC CONTRACTILITY

University Of Cincinnati, Cincinnati OH

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Abstract

DESCRIPTION (adapted from the applicant's description): The central hypothesis of this proposal is that sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA) is a critical determinant of myocardial contractility. The proposal has four specific questions (aims). Specific aim 1: Are there homeostatic mechanisms within the cardiac myocyte that are capable of sensing perturbations in the level of SERCA and developing compensatory mechanisms? Specific aim 2: What are the functional consequences of increased or decreased SR calcium uptake on the overall calcium homeostasis within the cardiac myocyte? Specific aim 3: What are the functional consequences of altered SR calcium transport on myocardial performance. Specific aim 4: What is the role of SERCA in cardiac hypertrophy and heart failure? These questions will be studied in transgenic mice with an overexpression of SERCA (both SERCA2a and SERCA1a) and in transgenic mice with a decrease in SERCA (SERCA knockout mice (+/-)).