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Calcium is a second messenger that regulates almost all cellular functions. In cardiomyocytes, calcium plays an integral role in many functions including muscle contraction, gene expression, and cell death. Inositol 1,4,5-trisphosphate receptors (IP 3 Rs) are a family of calcium channels that are ubiquitously expressed in all tissues. In the heart, IP 3 Rs have been associated with regulation of cardiomyocyte function in response to a variety of neurohormonal agonists, including those implicated in cardiac disease. Notably, IP 3 R activity is thought to be essential for mediating the hypertrophic response to multiple stimuli including endothelin-1 and angiotensin II. In this review, we will explore the functional implications of IP 3 R activity in the heart in health and disease. [ABSTRACT FROM AUTHOR]

Tumor cells strategically down-regulate Fas receptor expression to evade immune attack and up-regulate expression of Fas ligand to promote apoptosis of infiltrating T lymphocytes. Many pathways leading to apoptotic cell death require calcium release from inositol 1,4,5-trisphosphate receptors (IP3Rs). Here, we show that Fas-dependent killing of Jurkat T lymphoma cells by SW620 colon cancer cells requires calcium release from IP3R. General suppression of IP3R signaling significantly reduced SW620-mediated Jurkat cell apoptosis. Significantly, a specific inhibitor of apoptotic calcium release from IP3R strongly blocked lymphocyte apoptosis. Thus, selective pharmacological targeting of apoptotic calcium release from IP3R may enhance tumor cell immunogenicity. [ABSTRACT FROM AUTHOR]