| First Author | Liu X | Year | 2017 |
| Journal | Oncotarget | Volume | 8 |
| Issue | 35 | Pages | 59345-59358 |
| PubMed ID | 28938641 | Mgi Jnum | J:264951 |
| Mgi Id | MGI:6198984 | Doi | 10.18632/oncotarget.19581 |
| Citation | Liu X, et al. (2017) Potential independent action of sigma receptor ligands through inhibition of the Kv2.1 channel. Oncotarget 8(35):59345-59358 |
| abstractText | The sigma-1 receptor (sigma1-R) and sigma-2 receptor (sigma2-R) are potential drug targets for treatment of cancer, pain, depression, retinal degeneration and other neuronal diseases. Previous reports show that sigma-1 receptor modulates the activities of multiple channels. We are interested in possible sigma receptor modulation of Kv2.1, a K(+) channel abundant in retinal photoreceptors. We tested the effect of established sigma receptor ligands on Kv2.1 channels which were stably expressed in HEK293 cells. Surprisingly, sigma1-R antagonists inhibited Kv2.1 currents in both wild type and sigma1-R knockout HEK293 cells that we engineered using the CRISPR/Cas9 technology. Moreover, PB28, a sigma1-R antagonist and also sigma2-R agonist, inhibited Kv2.1 in sigma1-R knockout cells, but this action was not blocked by the sigma2-R antagonists that did not have an effect on Kv2.1. We also observed inhibition of electroretinogram by PB28 in wild type as well as sigma1-R knockout mice. Thus, the results in this study indicate that the Kv2.1-inhibiting function of the sigma ligands is not sigma receptor dependent, suggesting a direct effect of these ligands on the Kv2.1 channel. |
