Integrative Physiology of the Plasma Membrane Calcium Pump Isoform 4 in the Healthy and Failing Heart

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Heart failure, which is a condition in which the heart is unable to pump sufficient blood throughout the body, and its early signs are a major cause of disability, reduced quality of life and death in our aging population. In order to develop better treatments we must increase our understanding of the genetic and molecular changes which lead to heart failure. Calcium is very important for the correct functioning of the heart and it is well know that disruption of calcium levels leads to cardiovascular complications. One of the proteins involved in the movement of calcium from heart cells is the plasma membrane calcium pump (PMCA); in this project we aim to find out how PMCA regulates the working of the heart. Specifically we will generate mice with modified expression of PMCA and determine whether this leads to changes in the structure and/or function of the heart. We use the mouse as a model system as it reflects the human heart and we are able to use tools similar to those used by clinicians to determine how well the heart is working.This research will improve our understanding of heart failure and may lead to potential new treatment strategies.