Carvedilol inhibits cADPR- and IP3-induced Ca2+ release
Spontaneous Ca2+ waves, also termed store-overload-induced Ca2+ release (SOICR), in cardiac cells can trigger ventricular arrhythmias especially in failing hearts. SOICR occurs when Ryanodine receptors (RyRs) are activated by an increase in sarcoplasmic reticulum (SR) luminal Ca2+. Carvedilol is one...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Scientific Publishers
2017
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| _version_ | 1797067661742440448 |
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| author | Morgan, A Bampali, K Ruas, M Factor, C Back, T Chen, S Galione, A |
| author_facet | Morgan, A Bampali, K Ruas, M Factor, C Back, T Chen, S Galione, A |
| author_sort | Morgan, A |
| collection | OXFORD |
| description | Spontaneous Ca2+ waves, also termed store-overload-induced Ca2+ release (SOICR), in cardiac cells can trigger ventricular arrhythmias especially in failing hearts. SOICR occurs when Ryanodine receptors (RyRs) are activated by an increase in sarcoplasmic reticulum (SR) luminal Ca2+. Carvedilol is one of the most effective drugs for preventing arrhythmias in patients with heart failure. Furthermore, carvedilol analogues with minimal β-blocking activity also block SOICR showing that SOICR-inhibiting activity is distinct from that for β-block. We show here that carvedilol is a potent inhibitor of cADPR-induced Ca2+ release in sea urchin egg homogenate. In addition, the carvedilol analog VK-II-86 with minimal β-blocking activity also suppresses cADPR-induced Ca2+ release. Carvedilol appeared to be a non-competitive antagonist of cADPR and could also suppress Ca2+ release by caffeine. These results are consistent with cADPR releasing Ca2+ in sea urchin eggs by sensitizing RyRs to Ca2+ involving a luminal Ca2+ activation mechanism. In addition to action on the RyR, we also observed inhibition of inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release by carvedilol suggesting a common mechanism between these evolutionarily related and conserved Ca2+ release channels. |
| first_indexed | 2024-03-06T21:59:33Z |
| format | Journal article |
| id | oxford-uuid:4e1c8c00-5fb7-4e66-b147-e31b595bfb65 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:59:33Z |
| publishDate | 2017 |
| publisher | American Scientific Publishers |
| record_format | dspace |
| spelling | oxford-uuid:4e1c8c00-5fb7-4e66-b147-e31b595bfb652022-03-26T15:59:22ZCarvedilol inhibits cADPR- and IP3-induced Ca2+ releaseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4e1c8c00-5fb7-4e66-b147-e31b595bfb65EnglishSymplectic Elements at OxfordAmerican Scientific Publishers2017Morgan, ABampali, KRuas, MFactor, CBack, TChen, SGalione, ASpontaneous Ca2+ waves, also termed store-overload-induced Ca2+ release (SOICR), in cardiac cells can trigger ventricular arrhythmias especially in failing hearts. SOICR occurs when Ryanodine receptors (RyRs) are activated by an increase in sarcoplasmic reticulum (SR) luminal Ca2+. Carvedilol is one of the most effective drugs for preventing arrhythmias in patients with heart failure. Furthermore, carvedilol analogues with minimal β-blocking activity also block SOICR showing that SOICR-inhibiting activity is distinct from that for β-block. We show here that carvedilol is a potent inhibitor of cADPR-induced Ca2+ release in sea urchin egg homogenate. In addition, the carvedilol analog VK-II-86 with minimal β-blocking activity also suppresses cADPR-induced Ca2+ release. Carvedilol appeared to be a non-competitive antagonist of cADPR and could also suppress Ca2+ release by caffeine. These results are consistent with cADPR releasing Ca2+ in sea urchin eggs by sensitizing RyRs to Ca2+ involving a luminal Ca2+ activation mechanism. In addition to action on the RyR, we also observed inhibition of inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release by carvedilol suggesting a common mechanism between these evolutionarily related and conserved Ca2+ release channels. |
| spellingShingle | Morgan, A Bampali, K Ruas, M Factor, C Back, T Chen, S Galione, A Carvedilol inhibits cADPR- and IP3-induced Ca2+ release |
| title | Carvedilol inhibits cADPR- and IP3-induced Ca2+ release |
| title_full | Carvedilol inhibits cADPR- and IP3-induced Ca2+ release |
| title_fullStr | Carvedilol inhibits cADPR- and IP3-induced Ca2+ release |
| title_full_unstemmed | Carvedilol inhibits cADPR- and IP3-induced Ca2+ release |
| title_short | Carvedilol inhibits cADPR- and IP3-induced Ca2+ release |
| title_sort | carvedilol inhibits cadpr and ip3 induced ca2 release |
| work_keys_str_mv | AT morgana carvedilolinhibitscadprandip3inducedca2release AT bampalik carvedilolinhibitscadprandip3inducedca2release AT ruasm carvedilolinhibitscadprandip3inducedca2release AT factorc carvedilolinhibitscadprandip3inducedca2release AT backt carvedilolinhibitscadprandip3inducedca2release AT chens carvedilolinhibitscadprandip3inducedca2release AT galionea carvedilolinhibitscadprandip3inducedca2release |