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Kockskamper, J; Seidlmayer, L; Walther, S; Hellenkamp, K; Maier, LS; Pieske, B.
Endothelin-1 enhances nuclear Ca2+ transients in atrial myocytes through Ins(1,4,5)P3-dependent Ca2+ release from perinuclear Ca2+ stores.
J Cell Sci. 2008; 121(Pt 2):186-195
Doi: 10.1242/jcs.021386
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- Leading authors Med Uni Graz
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Kockskämper Jens
- Co-authors Med Uni Graz
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Pieske Burkert Mathias
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Walther Stefanie
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- Abstract:
- Nuclear Ca2+ plays a key role in the regulation of gene expression. Inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3)] 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)P3-induced Ca(2+) 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)P3 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)P3 signalling and might contribute to excitation-transcription coupling.
- Find related publications in this database (using NLM MeSH Indexing)
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Animals -
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Calcium - metabolism
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Calcium Signaling -
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Cell Nucleus - metabolism
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Cytoplasm - metabolism
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Endothelin-1 - biosynthesis
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Heart Atria - metabolism
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Inositol 1,4,5-Trisphosphate - metabolism
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Inositol 1,4,5-Trisphosphate Receptors - metabolism
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Kinetics -
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Microscopy, Confocal -
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Models, Biological -
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Muscle Cells - metabolism
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Rabbits -
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Sarcoplasmic Reticulum - metabolism
- Find related publications in this database (Keywords)
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endothelin
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inositol (1
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)-trisphosphate
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calcium
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nucleus
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myocyte