Regulation of Kv4.2 A-type potassium channels in HEK 293 cells by hypoxia
We previously observed that A-type potassium currents were decreased and membrane excitability increased in hippocampal dentate granule cells after neonatal global hypoxia associated with seizures. Here, we studied the effects of hypoxia on the function and expression of Kv4.2 and Kv4.3 α subunit c...
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| Format: | Article |
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Frontiers Media S.A.
2014-10-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00329/full |
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| author | Yu-Qiang eLiu Wen-Xian eHuang Russell M Sanchez Jia-Wei eMin Jiang-Jian eHu Xiao-Hua eHe Bi-Wen ePeng |
| author_facet | Yu-Qiang eLiu Wen-Xian eHuang Russell M Sanchez Jia-Wei eMin Jiang-Jian eHu Xiao-Hua eHe Bi-Wen ePeng |
| author_sort | Yu-Qiang eLiu |
| collection | DOAJ |
| description | We previously observed that A-type potassium currents were decreased and membrane excitability increased in hippocampal dentate granule cells after neonatal global hypoxia associated with seizures. Here, we studied the effects of hypoxia on the function and expression of Kv4.2 and Kv4.3 α subunit channels, which encode rapidly inactivating A-type K currents, in transfected HEK293 cells to determine if hypoxia alone could regulate IA in vitro. Global hypoxia in neonatal rat pups resulted in early decreased hippocampal expression of Kv4.2 mRNA and protein with 6 or 12 hours post-hypoxia. Whole-cell voltage-clamp recordings revealed that similar times after hypoxia (1%) in vitro decreased peak currents mediated by recombinant Kv4.2 but not Kv4.3 channels. Hypoxia had no significant effect on the voltage-dependencies of activation and inactivation of Kv4.2 channels, but increased the time constant of activation. The same result was observed when Kv4.2 and Kv4.3 channels were co-expressed in a 1:1 ratio. These data suggested that hypoxia directly modulates A-type potassium channels of the subfamily typically expressed in principal hippocampal neurons, and does so in a manner to decrease function. Given the role of IA to slow action potential firing, these data are consistent with a direct effect of hypoxia to decrease IA as a mechanism of increased neuronal excitability and promotion of seizures. |
| first_indexed | 2024-04-13T14:00:50Z |
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| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-13T14:00:50Z |
| publishDate | 2014-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-73fbe21d63f04dd28a394614613ba9642022-12-22T02:44:03ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022014-10-01810.3389/fncel.2014.00329112420Regulation of Kv4.2 A-type potassium channels in HEK 293 cells by hypoxiaYu-Qiang eLiu0Wen-Xian eHuang1Russell M Sanchez2Jia-Wei eMin3Jiang-Jian eHu4Xiao-Hua eHe5Bi-Wen ePeng6School of Basic Medical Sciences Wuhan UniversitySchool of Basic Medical Sciences Wuhan UniversityCollege of Medicine, Texas A&M Health Science Center, Neuroscience Institute, Scott & White Hospital, & Central Texas Veterans Health Care SystemSchool of Basic Medical Sciences Wuhan UniversitySchool of Basic Medical Sciences Wuhan UniversitySchool of Basic Medical Sciences Wuhan UniversitySchool of Basic Medical Sciences Wuhan UniversityWe previously observed that A-type potassium currents were decreased and membrane excitability increased in hippocampal dentate granule cells after neonatal global hypoxia associated with seizures. Here, we studied the effects of hypoxia on the function and expression of Kv4.2 and Kv4.3 α subunit channels, which encode rapidly inactivating A-type K currents, in transfected HEK293 cells to determine if hypoxia alone could regulate IA in vitro. Global hypoxia in neonatal rat pups resulted in early decreased hippocampal expression of Kv4.2 mRNA and protein with 6 or 12 hours post-hypoxia. Whole-cell voltage-clamp recordings revealed that similar times after hypoxia (1%) in vitro decreased peak currents mediated by recombinant Kv4.2 but not Kv4.3 channels. Hypoxia had no significant effect on the voltage-dependencies of activation and inactivation of Kv4.2 channels, but increased the time constant of activation. The same result was observed when Kv4.2 and Kv4.3 channels were co-expressed in a 1:1 ratio. These data suggested that hypoxia directly modulates A-type potassium channels of the subfamily typically expressed in principal hippocampal neurons, and does so in a manner to decrease function. Given the role of IA to slow action potential firing, these data are consistent with a direct effect of hypoxia to decrease IA as a mechanism of increased neuronal excitability and promotion of seizures.http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00329/fullhypoxiapatch clampin vitrocultureA-current |
| spellingShingle | Yu-Qiang eLiu Wen-Xian eHuang Russell M Sanchez Jia-Wei eMin Jiang-Jian eHu Xiao-Hua eHe Bi-Wen ePeng Regulation of Kv4.2 A-type potassium channels in HEK 293 cells by hypoxia Frontiers in Cellular Neuroscience hypoxia patch clamp in vitro culture A-current |
| title | Regulation of Kv4.2 A-type potassium channels in HEK 293 cells by hypoxia |
| title_full | Regulation of Kv4.2 A-type potassium channels in HEK 293 cells by hypoxia |
| title_fullStr | Regulation of Kv4.2 A-type potassium channels in HEK 293 cells by hypoxia |
| title_full_unstemmed | Regulation of Kv4.2 A-type potassium channels in HEK 293 cells by hypoxia |
| title_short | Regulation of Kv4.2 A-type potassium channels in HEK 293 cells by hypoxia |
| title_sort | regulation of kv4 2 a type potassium channels in hek 293 cells by hypoxia |
| topic | hypoxia patch clamp in vitro culture A-current |
| url | http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00329/full |
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