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- W42686867 abstract "Introduction : Calcineurin is activated by Ca 2+ /calmodulin and promotes pathological remodeling of the heart. In many cell types, store-operated calcium (SOC) entry, a process triggered by depletion of ER Ca stores, plays an obligate role in repleting Ca stores, and hence, in subsequent sustained increases in intracellular Ca. Little is known regarding SOC Ca influx in heart or its role in stress responsiveness. Methods and Results : Using RT-PCR, immunofluorescence staining, and Western blot methods, we found that Stim1, a recently identified molecular component of the SOC channel, is expressed in both neonatal rat ventricular myocytes (NRVMs) and adult myocytes. Working with isolated cells, we used Fura-2 to measure SOC Ca influx, finding that this mechanism does, in fact, exist in cardiomyocytes. However, SOC Ca influx was substantially more robust in neonatal myocytes than adult. Given that SOC current was prominent in neonatal cells, we tested ventricular myocytes isolated from calcineurin-transgenic mice, a model where the fetal gene program is prominently activated. Here, we found that Stim1 is up-regulated (1.9±0.4-fold, p<0.05). Treatment of NRVMs with angiotensin II (100nM) elicited similar increases in Stim1 (2.3±0.2-fold, p<0.01). To probe the molecular basis of cardiac SOC current, we expressed mutant (D76A, constitutively active; ΔERM, dominant negative) forms of human Stim1 in NRVMs. D76A markedly increased SOC Ca influx triggered by thapsigargin (2μM) or cyclopiazonic acid (50μM). In contrast, ΔERM blocked SOC Ca influx. Conclusion: SOC Ca entry exists prominently in neonatal cardiomyocytes but is down-regulated in adult cells. Stim1 participates in SOC current and is up-regulated during hypertrophic transformation of the myocardium. We conclude that SOC Ca currents are part of the fetal gene program in heart and may play a significant role in the sustained Ca overload of heart failure. This research has received full or partial funding support from the American Heart Association, AHA South Central Affiliate (Arkansas, New Mexico, Oklahoma & Texas)." @default.
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- W42686867 date "2008-10-28" @default.
- W42686867 modified "2023-09-26" @default.
- W42686867 title "Abstract 1508: Stim1-Mediated Store-Operated Calcium (SOC) Influx in Calcineurin-Dependent Cardiac Hypertrophy" @default.
- W42686867 doi "https://doi.org/10.1161/circ.118.suppl_18.s_339-d" @default.
- W42686867 hasPublicationYear "2008" @default.
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