Inositol 1,4,5-trisphosphate supports the arrhythmogenic action of endothelin-1 on ventricular cardiac myocytes.
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...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2006
|
| _version_ | 1797066391114743808 |
|---|---|
| author | Proven, A Roderick, H Conway, S Berridge, M Horton, J Capper, S Bootman, MD |
| author_facet | Proven, A Roderick, H Conway, S Berridge, M Horton, J Capper, S Bootman, MD |
| author_sort | Proven, A |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T21:41:22Z |
| format | Journal article |
| id | oxford-uuid:480e5336-2181-4a37-ba4a-c48327cc2a6b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:41:22Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:480e5336-2181-4a37-ba4a-c48327cc2a6b2022-03-26T15:23:25ZInositol 1,4,5-trisphosphate supports the arrhythmogenic action of endothelin-1 on ventricular cardiac myocytes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:480e5336-2181-4a37-ba4a-c48327cc2a6bEnglishSymplectic Elements at Oxford2006Proven, ARoderick, HConway, SBerridge, MHorton, JCapper, SBootman, MDAlthough 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. |
| spellingShingle | Proven, A Roderick, H Conway, S Berridge, M Horton, J Capper, S Bootman, MD Inositol 1,4,5-trisphosphate supports the arrhythmogenic action of endothelin-1 on ventricular cardiac myocytes. |
| title | Inositol 1,4,5-trisphosphate supports the arrhythmogenic action of endothelin-1 on ventricular cardiac myocytes. |
| title_full | Inositol 1,4,5-trisphosphate supports the arrhythmogenic action of endothelin-1 on ventricular cardiac myocytes. |
| title_fullStr | Inositol 1,4,5-trisphosphate supports the arrhythmogenic action of endothelin-1 on ventricular cardiac myocytes. |
| title_full_unstemmed | Inositol 1,4,5-trisphosphate supports the arrhythmogenic action of endothelin-1 on ventricular cardiac myocytes. |
| title_short | Inositol 1,4,5-trisphosphate supports the arrhythmogenic action of endothelin-1 on ventricular cardiac myocytes. |
| title_sort | inositol 1 4 5 trisphosphate supports the arrhythmogenic action of endothelin 1 on ventricular cardiac myocytes |
| work_keys_str_mv | AT provena inositol145trisphosphatesupportsthearrhythmogenicactionofendothelin1onventricularcardiacmyocytes AT roderickh inositol145trisphosphatesupportsthearrhythmogenicactionofendothelin1onventricularcardiacmyocytes AT conways inositol145trisphosphatesupportsthearrhythmogenicactionofendothelin1onventricularcardiacmyocytes AT berridgem inositol145trisphosphatesupportsthearrhythmogenicactionofendothelin1onventricularcardiacmyocytes AT hortonj inositol145trisphosphatesupportsthearrhythmogenicactionofendothelin1onventricularcardiacmyocytes AT cappers inositol145trisphosphatesupportsthearrhythmogenicactionofendothelin1onventricularcardiacmyocytes AT bootmanmd inositol145trisphosphatesupportsthearrhythmogenicactionofendothelin1onventricularcardiacmyocytes |