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First published online 18 December 2007
doi: 10.1242/jcs.021386

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Endothelin-1 enhances nuclear Ca²⁺ transients in atrial myocytes through Ins(1,4,5)P₃-dependent Ca²⁺ release from perinuclear Ca²⁺ stores

¹ Department of Cardiology and Pneumology, University Medicine Göttingen, Germany
² Department of Cardiology, Medical University of Graz, Auenbruggerplatz 15, A-8036 Graz, Austria

^* Author for correspondence (e-mail: jens.kockskaemper{at}meduni-graz.at)

Accepted 25 October 2007

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 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)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 β-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.

Key words: Endothelin, Inositol (1,4,5)-trisphosphate, Calcium, Nucleus, Myocyte

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