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Role of $Na^{+}/Ca^{2+}$exchange in endothelin-1-induced increases in $Ca^{2+}$transient and contractility in rabbit ventricular myocytes: pharmacological analysis with KB-R7943
| Content Provider | Scilit |
|---|---|
| Author | Yang, Huang-Tian Sakurai, Kiyoharu Sugawara, Hiromi Watanabe, Tomoo Norota, Ikuo Endoh, Masao |
| Copyright Year | 1999 |
| Description | Journal: British Journal of Pharmacology 1. The effects of endothelin-1 (ET-1) on intracellular Ca2+ ion level and cell contraction were simultaneously investigated in rabbit ventricular cardiac myocytes loaded with indo-1/A1. The role of Na+/Ca2+ exchange in ET-1-induced positive inotropic effect (PIE) was examined by using KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulphonate), a selective inhibitor of reverse mode Na+/Ca2+ exchange. 2. ET-1 at 0.3 pM - 1 nM increased cell contraction and Ca2+ transient (CaT) with EC50 values of 2.9 pM and 1.2 pM, respectively, and the increase in amplitude of CaT was much smaller relative to the PIE: ET-1 at 1 nM increased peak cell shortening by 237%, while it increased peak CaT by 167%. For a given level of PIE, ET-1-induced increase in CaT was much smaller than that induced by elevation of [Ca2+]o and by isoprenaline. Therefore, ET-1 shifted the relationship between peak CaT and cell shortening to the left relative to the relationship for increase in [Ca2+]o, an indication that ET-1 increased myofibrillar Ca2+ sensitivity. 3. KB-R7943 at 0.1 microM and higher inhibited contraction and CaT induced by 0.1 nM ET-1 and at 0.3 microM it abolished the increase in CaT while inhibiting the PIE by 48.1%. Over concentration range of 0.1-0.3 microM, KB-R7943 neither inhibited baseline contraction and CaT nor the isoprenaline-induced response, although at 1 microM and higher it had a significant inhibitory action on these responses. 4. These results indicate that in rabbit ventricular myocytes both increases in CaT and myofibrillar Ca2+ sensitivity contribute to the ET-induced PIE, and the activation of reverse mode Na+/Ca2+ exchange may play a crucial role in increase in CaT induced by ET-1 in rabbit ventricular cardiac myocytes. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1565953/pdf |
| Ending Page | 1795 |
| Page Count | 11 |
| Starting Page | 1785 |
| e-ISSN | 14765381 |
| DOI | 10.1038/sj.bjp.0702454 |
| Journal | British Journal of Pharmacology |
| Issue Number | 8 |
| Volume Number | 126 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 1999-04-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: British Journal of Pharmacology Biochemistry and Molecular Biology Kb-r7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea Methanesulphonate) Na+/ca2+ Exchanger Adult Rabbit Ventricular Cardiac Myocytes |
| Content Type | Text |
| Resource Type | Article |
