Nicotinic acid adenine dinucleotide phosphate (NAADP)-mediated calcium signaling and arrhythmias in the heart evoked by β-adrenergic stimulation
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Nicotinic acid adenine dinucleotide phosphate (NAADP)-mediated calcium signaling and arrhythmias in the heart evoked by β-adrenergic stimulation. / Nebel, Merle; Schwoerer, Alexander P; Warszta, Dominik; Siebrands, Cornelia C; Limbrock, Ann-Christin; Swarbrick, Joanna M; Fliegert, Ralf; Weber, Karin; Bruhn, Sören; Hohenegger, Martin; Geisler, Anne; Herich, Lena; Schlegel, Susan; Carrier, Lucie; Eschenhagen, Thomas; Potter, Barry V L; Ehmke, Heimo; Guse, Andreas H.
In: J BIOL CHEM, Vol. 288, No. 22, 31.05.2013, p. 16017-30.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Nicotinic acid adenine dinucleotide phosphate (NAADP)-mediated calcium signaling and arrhythmias in the heart evoked by β-adrenergic stimulation
AU - Nebel, Merle
AU - Schwoerer, Alexander P
AU - Warszta, Dominik
AU - Siebrands, Cornelia C
AU - Limbrock, Ann-Christin
AU - Swarbrick, Joanna M
AU - Fliegert, Ralf
AU - Weber, Karin
AU - Bruhn, Sören
AU - Hohenegger, Martin
AU - Geisler, Anne
AU - Herich, Lena
AU - Schlegel, Susan
AU - Carrier, Lucie
AU - Eschenhagen, Thomas
AU - Potter, Barry V L
AU - Ehmke, Heimo
AU - Guse, Andreas H
PY - 2013/5/31
Y1 - 2013/5/31
N2 - Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most potent Ca(2+)-releasing second messenger known to date. Here, we report a new role for NAADP in arrhythmogenic Ca(2+) release in cardiac myocytes evoked by β-adrenergic stimulation. Infusion of NAADP into intact cardiac myocytes induced global Ca(2+) signals sensitive to inhibitors of both acidic Ca(2+) stores and ryanodine receptors and to NAADP antagonist BZ194. Furthermore, in electrically paced cardiac myocytes BZ194 blocked spontaneous diastolic Ca(2+) transients caused by high concentrations of the β-adrenergic agonist isoproterenol. Ca(2+) transients were recorded both as increases of the free cytosolic Ca(2+) concentration and as decreases of the sarcoplasmic luminal Ca(2+) concentration. Importantly, NAADP antagonist BZ194 largely ameliorated isoproterenol-induced arrhythmias in awake mice. We provide strong evidence that NAADP-mediated modulation of couplon activity plays a role for triggering spontaneous diastolic Ca(2+) transients in isolated cardiac myocytes and arrhythmias in the intact animal. Thus, NAADP signaling appears an attractive novel target for antiarrhythmic therapy.
AB - Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most potent Ca(2+)-releasing second messenger known to date. Here, we report a new role for NAADP in arrhythmogenic Ca(2+) release in cardiac myocytes evoked by β-adrenergic stimulation. Infusion of NAADP into intact cardiac myocytes induced global Ca(2+) signals sensitive to inhibitors of both acidic Ca(2+) stores and ryanodine receptors and to NAADP antagonist BZ194. Furthermore, in electrically paced cardiac myocytes BZ194 blocked spontaneous diastolic Ca(2+) transients caused by high concentrations of the β-adrenergic agonist isoproterenol. Ca(2+) transients were recorded both as increases of the free cytosolic Ca(2+) concentration and as decreases of the sarcoplasmic luminal Ca(2+) concentration. Importantly, NAADP antagonist BZ194 largely ameliorated isoproterenol-induced arrhythmias in awake mice. We provide strong evidence that NAADP-mediated modulation of couplon activity plays a role for triggering spontaneous diastolic Ca(2+) transients in isolated cardiac myocytes and arrhythmias in the intact animal. Thus, NAADP signaling appears an attractive novel target for antiarrhythmic therapy.
KW - Adrenergic beta-Agonists
KW - Animals
KW - Arrhythmias, Cardiac
KW - Calcium Signaling
KW - Cells, Cultured
KW - Isoproterenol
KW - Mice
KW - Myocardium
KW - Myocytes, Cardiac
KW - NADP
KW - Nicotinic Acids
KW - Ryanodine Receptor Calcium Release Channel
KW - Sarcoplasmic Reticulum
U2 - 10.1074/jbc.M112.441246
DO - 10.1074/jbc.M112.441246
M3 - SCORING: Journal article
C2 - 23564460
VL - 288
SP - 16017
EP - 16030
JO - J BIOL CHEM
JF - J BIOL CHEM
SN - 0021-9258
IS - 22
ER -