ATP modulation of ATP-sensitive potassium channel ATP sensitivity varies with the type of SUR subunit.
ATP-sensitive potassium (K(ATP)) channels comprise Kir and SUR subunits. Using recombinant K(ATP) channels expressed in Xenopus oocytes, we observed that MgATP (100 microm) block of Kir6.2/SUR2A currents gradually declined with time, whereas inhibition of Kir6.2/SUR1 or Kir6.2DeltaC36 currents did n...
| Main Authors: | , |
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| Format: | Journal article |
| Language: | English |
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2001
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| _version_ | 1797075357464002560 |
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| author | Song, D Ashcroft, F |
| author_facet | Song, D Ashcroft, F |
| author_sort | Song, D |
| collection | OXFORD |
| description | ATP-sensitive potassium (K(ATP)) channels comprise Kir and SUR subunits. Using recombinant K(ATP) channels expressed in Xenopus oocytes, we observed that MgATP (100 microm) block of Kir6.2/SUR2A currents gradually declined with time, whereas inhibition of Kir6.2/SUR1 or Kir6.2DeltaC36 currents did not change. The decline in Kir6.2/SUR2A ATP sensitivity was not observed in Mg(2+) free solution and was blocked by the phosphatidylinositol (PI) 3-kinase inhibitors LY 294002 (10 microm) and wortmannin (100 microm), and by neomycin (100 microm). These results suggest that a MgATP-dependent synthesis of membrane phospholipids produces a secondary decrease in the ATP sensitivity of Kir6.2/SUR2A. Direct application of the phospholipids PI 4,5-bisphosphate and PI 3,4,5-trisphosphate in the presence of 100 microm MgATP activated all three types of channel, but the response was faster for Kir6.2/SUR2A. Chimeric studies indicate that the different responses of Kir6.2/SUR2A and Kir6.2/SUR1 are mediated by the first six transmembrane domains of SUR. The MgATP-dependent loss of ATP sensitivity of Kir6.2/SUR2A was enhanced by the actin filament disrupter cytochalasin and blocked by phalloidin (which stabilizes the cytoskeleton). Phalloidin did not block the effect of PI 3,4,5-trisphosphate. This suggests that MgATP may cause disruption of the cytoskeleton, leading to enhanced membrane phospholipid levels (or better targeting to the K(ATP) channel) and thus to decreased channel ATP sensitivity. |
| first_indexed | 2024-03-06T23:49:19Z |
| format | Journal article |
| id | oxford-uuid:720acd6c-736a-4401-89e8-b064aead7940 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:49:19Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:720acd6c-736a-4401-89e8-b064aead79402022-03-26T19:47:34ZATP modulation of ATP-sensitive potassium channel ATP sensitivity varies with the type of SUR subunit.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:720acd6c-736a-4401-89e8-b064aead7940EnglishSymplectic Elements at Oxford2001Song, DAshcroft, FATP-sensitive potassium (K(ATP)) channels comprise Kir and SUR subunits. Using recombinant K(ATP) channels expressed in Xenopus oocytes, we observed that MgATP (100 microm) block of Kir6.2/SUR2A currents gradually declined with time, whereas inhibition of Kir6.2/SUR1 or Kir6.2DeltaC36 currents did not change. The decline in Kir6.2/SUR2A ATP sensitivity was not observed in Mg(2+) free solution and was blocked by the phosphatidylinositol (PI) 3-kinase inhibitors LY 294002 (10 microm) and wortmannin (100 microm), and by neomycin (100 microm). These results suggest that a MgATP-dependent synthesis of membrane phospholipids produces a secondary decrease in the ATP sensitivity of Kir6.2/SUR2A. Direct application of the phospholipids PI 4,5-bisphosphate and PI 3,4,5-trisphosphate in the presence of 100 microm MgATP activated all three types of channel, but the response was faster for Kir6.2/SUR2A. Chimeric studies indicate that the different responses of Kir6.2/SUR2A and Kir6.2/SUR1 are mediated by the first six transmembrane domains of SUR. The MgATP-dependent loss of ATP sensitivity of Kir6.2/SUR2A was enhanced by the actin filament disrupter cytochalasin and blocked by phalloidin (which stabilizes the cytoskeleton). Phalloidin did not block the effect of PI 3,4,5-trisphosphate. This suggests that MgATP may cause disruption of the cytoskeleton, leading to enhanced membrane phospholipid levels (or better targeting to the K(ATP) channel) and thus to decreased channel ATP sensitivity. |
| spellingShingle | Song, D Ashcroft, F ATP modulation of ATP-sensitive potassium channel ATP sensitivity varies with the type of SUR subunit. |
| title | ATP modulation of ATP-sensitive potassium channel ATP sensitivity varies with the type of SUR subunit. |
| title_full | ATP modulation of ATP-sensitive potassium channel ATP sensitivity varies with the type of SUR subunit. |
| title_fullStr | ATP modulation of ATP-sensitive potassium channel ATP sensitivity varies with the type of SUR subunit. |
| title_full_unstemmed | ATP modulation of ATP-sensitive potassium channel ATP sensitivity varies with the type of SUR subunit. |
| title_short | ATP modulation of ATP-sensitive potassium channel ATP sensitivity varies with the type of SUR subunit. |
| title_sort | atp modulation of atp sensitive potassium channel atp sensitivity varies with the type of sur subunit |
| work_keys_str_mv | AT songd atpmodulationofatpsensitivepotassiumchannelatpsensitivityvarieswiththetypeofsursubunit AT ashcroftf atpmodulationofatpsensitivepotassiumchannelatpsensitivityvarieswiththetypeofsursubunit |