期刊
JOURNAL OF CELL SCIENCE
卷 121, 期 2, 页码 186-195出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.021386
关键词
endothelin; inositol (1,4,5)-trisphosphate; calcium; nucleus; myocyte
类别
Nuclear Ca2+ plays a key role in the regulation of gene expression. Inositol ( 1,4,5)-trisphosphate [Ins( 1,4,5) P-3)] might be an important regulator of nuclear Ca2+ but its contribution to nuclear Ca2+ signalling in adult cardiomyocytes remains elusive. We tested the hypothesis that endothelin-1 enhances nuclear Ca2+ concentration transients (CaTs) in rabbit atrial myocytes through Ins( 1,4,5) P-3-induced Ca2+ release from perinuclear stores. Cytoplasmic and nuclear CaTs were measured simultaneously in electrically stimulated atrial myocytes using confocal Ca2+ imaging. Nuclear CaTs were significantly slower than cytoplasmic CaTs, indicative of compartmentalisation of intracellular Ca2+ signalling. Endothelin-1 elicited a preferential ( 10 nM) or a selective (0.1 nM) increase in nuclear versus cytoplasmic CaTs. This effect was abolished by inhibition of endothelin-1 receptors, phospholipase C and Ins( 1,4,5) P-3 receptors. Fractional Ca2+ release from the sarcoplasmic reticulum and perinuclear stores was increased by endothelin-1 at an otherwise unaltered Ca2+ load. Comparable increases of cytoplasmic CaTs induced by beta-adrenoceptor stimulation or elevation of extracellular Ca2+ could not mimic the endothelin-1 effects on nuclear CaTs, suggesting that endothelin-1 specifically modulates nuclear Ca2+ signalling. Thus, endothelin-1 enhances nuclear CaTs in atrial myocytes by increasing fractional Ca2+ release from perinuclear stores. This effect is mediated by the coupling of endothelin receptor A to PLC-Ins( 1,4,5) P-3 signalling and might contribute to excitation-transcription coupling.
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