Abstract 207: Electrically-induced Calcium Handling in Human Cardiac Progenitor Cells

Abstract

The discovery of a resident population of cardiac stem cells known as cardiac progenitor cells (CPCs) has raised the question of the mechanisms involved in regenerative properties of this niche of cells. The physiology of human CPCs is not well understood, and a thorough understanding of the Ca 2+ handling ability of these cells is crucial in order to fully realize their regenerative potential. Therefore, to characterize the mechanism of electrically-induced Ca 2+ handling in human CPCs, we have used cells loaded with fluo-4 calcium dye and imaged using confocal microscopy to determine the spatial and temporal profile of cytosolic Ca 2+ upon electrical stimulation. Upon activation of electrical stimulation, a large increase in cytosolic Ca 2+ was observed followed by oscillations of the cytosolic Ca 2+ . The electrically-induced Ca 2+ oscillations were found to be dependent on the activity of L-type Ca 2+ channels (LTCC) and the presence of extracellular Ca 2+ . Furthermore, these oscillations could be abolished by pre-treatment of the cells with the inositol 1,4,5-trisphosphate receptor (IP 3 R) antagonist 2-APB. High-speed confocal imaging of the electrically-induced Ca 2+ oscillations in hCPCs revealed that these cells oscillate in a Ca 2+ wave-like fashion with activity originating in isolated regions of the cell and propagating throughout the cytosol and nucleus. In conclusion, we propose that Ca 2+ -dependent regulatory mechanisms can be exploited to influence their differentiation potential leading to improved function in cardiac regenerative medicine.