Inositol 1,4,5-trisphosphate Supports the Arrhythmogenic Action of Endothelin-1 on Ventricular Cardiac Myocytes.
From: Calcium Group, Laboratory of Molecular Signalling, Babraham Institute, Babraham, Cambridge, CB2 4AT, UK.
Journal of cell science
- Publish Date: Aug 2006
- ISSN: 0021-9533
- Volume: 119
- Issue: Pt 16
- Pages: 3363-75
- Medium: Print
- Language: English
- Citation (JAMA): Proven Andrew, Roderick H Llewelyn, Conway Stuart J, et al. Inositol 1,4,5-trisphosphate Supports the Arrhythmogenic Action of Endothelin-1 on Ventricular Cardiac Myocytes.. J. Cell. Sci. Aug 2006;119:3363-75
Abstract
Although ventricular cardiomyocytes express inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] receptors, it is unclear how these Ca2+ channels contribute to the effects of Gq-coupled agonists. Endothelin-1 augmented the amplitude of pacing-evoked Ca2+ signals (positive inotropy), and caused an increasing frequency of spontaneous diastolic Ca2+-release transients. Both effects of endothelin-1 were blocked by an antagonist of phospholipase C, suggesting that Ins(1,4,5)P3 and/or diacylglycerol production was necessary. The endothelin-1-mediated spontaneous Ca2+ transients were abolished by application of 2-aminoethoxydiphenyl borate (2-APB), an antagonist of Ins(1,4,5)P3 receptors. Incubation of electrically-paced ventricular myocytes with a membrane-permeant Ins(1,4,5)P3 ester provoked the occurrence of spontaneous diastolic Ca2+ transients with the same characteristics and sensitivity to 2-APB as the events stimulated by endothelin-1. In addition to evoking spontaneous Ca2+ transients, stimulation of ventricular myocytes with the Ins(1,4,5)P3 ester caused a positive inotropic effect. The effects of endothelin-1 were compared with two other stimuli, isoproterenol and digoxin, which are known to induce inotropy and spontaneous Ca2+ transients by overloading intracellular Ca2+ stores. The events evoked by isoproterenol and digoxin were dissimilar from those triggered by endothelin-1 in several ways. We propose that Ins(1,4,5)P3 receptors support the development of both inotropy and spontaneous pro-arrhythmic Ca2+ signals in ventricular myocytes stimulated with a Gq-coupled agonist.
Mesh Headings (Keywords): Animals, Arrhythmias, Cardiac, Boron Compounds, Calcium, Calcium Channels, Calcium Signaling, Digoxin, Endothelin-1, Heart Ventricles, Inositol 1,4,5-Trisphosphate, Inositol 1,4,5-Trisphosphate Receptors, Isoproterenol, Myocytes, Cardiac, Rats, Rats, Wistar, Receptors, Cytoplasmic and Nuclear, Type C Phospholipases
Check for Full Text / PubMed Unique Identifier (PMID): 16882691
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