Activation of a calcium-sensing receptor (Ca-SR) leads to increased intracellular calcium concentration and altered cellular activities. The expression of Ca-SR has been identified in both nonexcitable and excitable cells, including neurons and smooth muscle cells. Whether Ca-SR was expressed and functioning in cardiac myocytes remained unclear. In the present study, the transcripts of Ca-SR were identified in rat heart tissues usingRT-PCR that was further confirmed by sequence analysis. Ca-SR proteins were detected in rat ventricular and atrial tissues as well as in isolated cardiac myocytes. Anti-(Ca-SR) Ig did not detect any specific bands after preadsorption with standard Ca-SR antigens. An immunohistochemistry study revealed the presence of Ca-SR in rat cardiac as well as other tissues. An increase in extracellular calcium or gadolinium induced a concentration-dependent sustained increase in [Ca2+]i in isolated ventricular myocytes from adult rats. Spermine (1–10 mM) also increased [Ca2+]i. Pre-treatment of cardiac myocytes with thapsigargin or U73122 abolished the extracellular calcium, gadolinium or spermine-induced increase in [Ca2+]i. The blockade of Na+/Ca2+ exchanger or voltagedependent calcium channels did not alter the extracellular calcium-induced increase in [Ca2+]i. Finally, extracellular calcium, gadolinium and spermine all increased intracellular inositol 1,4,5-triphosphate (IP3) levels. Our results demonstrated that Ca-SR was expressed in cardiac tissue and cardiomyocytes and its function was regulated by extracellular calcium and spermine.

Calcium sensing receptors (CaSR) is a member of super-family of G-protein coupling receptors.This review first introduced the concept, construction features, distribution, functions, decision methods, moderators, ge-netic locus of CaSR and its relationship with some diseases concisely. Then this article described the investigation progressof CaSR in cardiovascular system intensively, including the expression pattern, role and signal pathways of CaSR in rat my-ocardium in normal, ischemia-reperfusion injury, apoptosis and cardiac hypertrophy; the role and mechanism of CaSR incalcium homostasis regulation of rat myocardium, endoplasmic reticulum (ER) stress and cardiac ischemic preconditioningand postconditioning. The metabolism rule, physiological significance and pathological action of polyamine in cardiac cells; the increase of CaSR expression in cardiac tissue of artherosclerosic rat and its effect on sensitivity to acute myocardial in-farction are also discussed. In the end, the research perspective of CaSR in cardiovascular system was anticipated.

The expression and function of calcium-sensingreceptor (CaSR) in differentiated THP-1 (human acutemonocytic leukemia cell line) cells are unknown currently.This study investigated above-mentioned issues usingTRAP staining, immunofluorescence staining, Westernblotting, ELISA, and Laser Confocal Scanning Microscopytechniques. We found that CaSR protein was expressed, andmainly located in the membrane and cytoplasm in differentiatedTHP-1 cells. Elevated extracellular calcium orGdCl3 (an agonist of CaSR) raised intracellular calciumconcentration. And this increase was inhibited or abolishedby NPS2390 (an inhibitor of CaSR), U73122 (a specificinhibitor of phospholipase C, PLC) or thapsigargin (a Ca2?-ATPase inhibitor). The extracellular GdCl3 elevation stimulatedboth of IL-1b and TNFa release, and this effect ofGdCl3 was inhibited by NPS2390. In conclusion, CaSR isfunctionally expressed in differentiated THP-1 cells, and theactivated CaSR contributes to intracellular calcium incrementthrough Gq-PLC-inositol triphosphate (IP3) pathwayand commits to cytokine secretion. These results suggestthat CaSR might be involved in a variety of pathologicalprocesses mediated by activated monocyte-macrophages.

The calcium-sensing receptor (CaR) is a G protein-coupled receptor. The CaR stimulation elicits phospholipaseC-mediated inositol triphosphate formation, leading to an elevation in the level of intracellular calcium released from endoplasmicreticulum (ER). Depletion of ER Ca2+ leads to ER stress, which is thought to induce apoptosis. Intracellular calciumoverload-induced apoptosis in cardiac myocytes during hypoxia–reoxygenation (H ?Re) has been demonstrated. However, thelinks between CaR, ER stress and apoptosis during H?Re are unclear. This study hypothesized that the CaR could induceapoptosis in neonatal rat cardiomyocytes during H?Re via the ER stress pathway. Neonatal rat cardiomyocytes were subjectedto 3 hr of hypoxia, followed by 6 hr of reoxygenation. CaR expression was elevated and the number of apoptotic cells wassignificantly increased, as shown by transferase-mediated dUTP nick end-labelling, with exposure to CaCl2, a CaR activator,during H?Re. The intracellular calcium concentration was significantly elevated and the Ca2+ concentration in the ER wasdramatically decreased during H?Re with CaCl2; both intracellular and ER calcium concentrations were detected by laserconfocal microscopy. Expression of GRP78 (glucose-regulated protein 78), the cleavage products of ATF6 (activating transcriptionfactor 6), phospho-PERK [pancreatic ER kinase (PKR)-like ER kinase], the activated fragments of caspase-12, andphospho-JNK (c-Jun NH2-terminal kinase) were increased following exposure to CaCl2 during H?Re. Our results confirmedthat the activated CaR can induce cardiomyocyte apoptosis via ER stress-associated apoptotic pathways during H? Re.