Functional study of the effect of phosphatase inhibitors on KCNQ4 channels expressed in Xenopus oocytes
Aim： KCNQ4 channels play an important part in adjusting the function of cochlear outer hair cells. The aim of this study was to investigate the effects of ser/thr phosphatase inhibitors on human KCNQ4 channels expressed in Xenopus laevis oocytes. Methods： Synthetic cRNA encoding human KCNQ4 channels...
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| Veröffentlicht in: | Acta pharmacologica Sinica 2009-09, Vol.30 (9), p.1220-1226 |
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| description | Aim： KCNQ4 channels play an important part in adjusting the function of cochlear outer hair cells. The aim of this study was to investigate the effects of ser/thr phosphatase inhibitors on human KCNQ4 channels expressed in Xenopus laevis oocytes. Methods： Synthetic cRNA encoding human KCNQ4 channels was injected into Xenopus oocytes. We used a two-electrode voltage clamp to measure the ion currents in the oocytes. Results： Wild-type KCNQ4 expressed in Xenopus oocytes showed the typical properties of slow activation kinetics and low threshold activation. The outward K~ current was almost completely blocked by a KCNQ4 blocker, linopirdine （0.25 mmol/L）. BIMI （a PKC inhibitor） prevented the effects of PMA （a PKC activator） on the KCNQ4 current, indicating that PKC may be involved in the regulation of KCNQ4 expressed in the Xenopus oocyte system. Treatment with the ser/thr phosphatase inhibitors, cyclosporine （2 pmol/L）, calyculin A （2 pmol/L） or okadaic acid （1 pmol/L）, caused a significant positive shift in V1/2 and a decrease in the conductance of KCNQ4 channels. The V1/2 was shifted from -14.6±0.5 to -6.4±0.4 mV by cyclosporine, -18.8±0.5 to -9.2_＋0.4 mV by calyculin A, and -14.1±0.5 to -0.7＋0.6 mV by okadaic acid. Moreover, the effects of these phosphatase inhibitors （okadaic acid or calyculin A） on the induction of a positive shift of V1/2 were augmented by further addition of PMA. Conclusion： These results indicate that ser/thr phosphatase inhibitors can induce a shift to more positive potentials of the activation curve of the KCNQ4 current. It is highly likely that the phosphatase functions to balance the phosphorylated state of substrate protein and thus has an important role in the regulation of human KCNQ4 channels expressed in Xenopus oocytes. |
| doi_str_mv | 10.1038/aps.2009.117 |
| format | Article |
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The aim of this study was to investigate the effects of ser/thr phosphatase inhibitors on human KCNQ4 channels expressed in Xenopus laevis oocytes. Methods： Synthetic cRNA encoding human KCNQ4 channels was injected into Xenopus oocytes. We used a two-electrode voltage clamp to measure the ion currents in the oocytes. Results： Wild-type KCNQ4 expressed in Xenopus oocytes showed the typical properties of slow activation kinetics and low threshold activation. The outward K~ current was almost completely blocked by a KCNQ4 blocker, linopirdine （0.25 mmol/L）. BIMI （a PKC inhibitor） prevented the effects of PMA （a PKC activator） on the KCNQ4 current, indicating that PKC may be involved in the regulation of KCNQ4 expressed in the Xenopus oocyte system. Treatment with the ser/thr phosphatase inhibitors, cyclosporine （2 pmol/L）, calyculin A （2 pmol/L） or okadaic acid （1 pmol/L）, caused a significant positive shift in V1/2 and a decrease in the conductance of KCNQ4 channels. The V1/2 was shifted from -14.6±0.5 to -6.4±0.4 mV by cyclosporine, -18.8±0.5 to -9.2_＋0.4 mV by calyculin A, and -14.1±0.5 to -0.7＋0.6 mV by okadaic acid. Moreover, the effects of these phosphatase inhibitors （okadaic acid or calyculin A） on the induction of a positive shift of V1/2 were augmented by further addition of PMA. Conclusion： These results indicate that ser/thr phosphatase inhibitors can induce a shift to more positive potentials of the activation curve of the KCNQ4 current. It is highly likely that the phosphatase functions to balance the phosphorylated state of substrate protein and thus has an important role in the regulation of human KCNQ4 channels expressed in Xenopus oocytes.</description><identifier>ISSN: 1671-4083</identifier><identifier>EISSN: 1745-7254</identifier><identifier>DOI: 10.1038/aps.2009.117</identifier><identifier>PMID: 19701239</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Action Potentials - drug effects ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Cyclosporine - pharmacology ; Humans ; Immunology ; Indoles - pharmacology ; Internal Medicine ; KCNQ Potassium Channels - drug effects ; Maleimides - pharmacology ; Medical Microbiology ; Okadaic Acid - pharmacology ; Oocytes - metabolism ; Original ; original-article ; Oxazoles - pharmacology ; Pharmacology/Toxicology ; Phosphoprotein Phosphatases - antagonists & inhibitors ; Phosphoric Monoester Hydrolases - antagonists & inhibitors ; Potassium Channel Blockers - pharmacology ; Protein Kinase C - antagonists & inhibitors ; Pyridines - pharmacology ; Vaccine ; Xenopus laevis ; 细胞表达 ; 酶抑制剂</subject><ispartof>Acta pharmacologica Sinica, 2009-09, Vol.30 (9), p.1220-1226</ispartof><rights>CPS and SIMM 2009</rights><rights>Copyright Nature Publishing Group Sep 2009</rights><rights>Copyright © 2009 CPS and SIMM 2009 CPS and SIMM</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-973d0921fced45220eaf88df51db0c23ce8f022b41066b5325b01c126c367ff3</citedby><cites>FETCH-LOGICAL-c475t-973d0921fced45220eaf88df51db0c23ce8f022b41066b5325b01c126c367ff3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/95561A/95561A.jpg</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007189/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007189/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19701239$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Su, Tzu-rong</creatorcontrib><creatorcontrib>Chen, Cay-huyen</creatorcontrib><creatorcontrib>Huang, Shih-jen</creatorcontrib><creatorcontrib>Lee, Chun-yi</creatorcontrib><creatorcontrib>Su, Mao-chang</creatorcontrib><creatorcontrib>Chen, Gwan-hong</creatorcontrib><creatorcontrib>Li, Shuan-yow</creatorcontrib><creatorcontrib>Yang, Jiann-jou</creatorcontrib><creatorcontrib>Lin, Min-jon</creatorcontrib><title>Functional study of the effect of phosphatase inhibitors on KCNQ4 channels expressed in Xenopus oocytes</title><title>Acta pharmacologica Sinica</title><addtitle>Acta Pharmacol Sin</addtitle><addtitle>Acta Pharmacologica Sinica</addtitle><description>Aim： KCNQ4 channels play an important part in adjusting the function of cochlear outer hair cells. The aim of this study was to investigate the effects of ser/thr phosphatase inhibitors on human KCNQ4 channels expressed in Xenopus laevis oocytes. Methods： Synthetic cRNA encoding human KCNQ4 channels was injected into Xenopus oocytes. We used a two-electrode voltage clamp to measure the ion currents in the oocytes. Results： Wild-type KCNQ4 expressed in Xenopus oocytes showed the typical properties of slow activation kinetics and low threshold activation. The outward K~ current was almost completely blocked by a KCNQ4 blocker, linopirdine （0.25 mmol/L）. BIMI （a PKC inhibitor） prevented the effects of PMA （a PKC activator） on the KCNQ4 current, indicating that PKC may be involved in the regulation of KCNQ4 expressed in the Xenopus oocyte system. Treatment with the ser/thr phosphatase inhibitors, cyclosporine （2 pmol/L）, calyculin A （2 pmol/L） or okadaic acid （1 pmol/L）, caused a significant positive shift in V1/2 and a decrease in the conductance of KCNQ4 channels. The V1/2 was shifted from -14.6±0.5 to -6.4±0.4 mV by cyclosporine, -18.8±0.5 to -9.2_＋0.4 mV by calyculin A, and -14.1±0.5 to -0.7＋0.6 mV by okadaic acid. Moreover, the effects of these phosphatase inhibitors （okadaic acid or calyculin A） on the induction of a positive shift of V1/2 were augmented by further addition of PMA. Conclusion： These results indicate that ser/thr phosphatase inhibitors can induce a shift to more positive potentials of the activation curve of the KCNQ4 current. It is highly likely that the phosphatase functions to balance the phosphorylated state of substrate protein and thus has an important role in the regulation of human KCNQ4 channels expressed in Xenopus oocytes.</description><subject>Action Potentials - drug effects</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cyclosporine - pharmacology</subject><subject>Humans</subject><subject>Immunology</subject><subject>Indoles - pharmacology</subject><subject>Internal Medicine</subject><subject>KCNQ Potassium Channels - drug effects</subject><subject>Maleimides - pharmacology</subject><subject>Medical Microbiology</subject><subject>Okadaic Acid - pharmacology</subject><subject>Oocytes - metabolism</subject><subject>Original</subject><subject>original-article</subject><subject>Oxazoles - pharmacology</subject><subject>Pharmacology/Toxicology</subject><subject>Phosphoprotein Phosphatases - antagonists & 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study of the effect of phosphatase inhibitors on KCNQ4 channels expressed in Xenopus oocytes</title><author>Su, Tzu-rong ; Chen, Cay-huyen ; Huang, Shih-jen ; Lee, Chun-yi ; Su, Mao-chang ; Chen, Gwan-hong ; Li, Shuan-yow ; Yang, Jiann-jou ; Lin, Min-jon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-973d0921fced45220eaf88df51db0c23ce8f022b41066b5325b01c126c367ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Action Potentials - drug effects</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cyclosporine - pharmacology</topic><topic>Humans</topic><topic>Immunology</topic><topic>Indoles - pharmacology</topic><topic>Internal Medicine</topic><topic>KCNQ Potassium Channels - drug effects</topic><topic>Maleimides - pharmacology</topic><topic>Medical Microbiology</topic><topic>Okadaic Acid - pharmacology</topic><topic>Oocytes - metabolism</topic><topic>Original</topic><topic>original-article</topic><topic>Oxazoles - pharmacology</topic><topic>Pharmacology/Toxicology</topic><topic>Phosphoprotein Phosphatases - antagonists & inhibitors</topic><topic>Phosphoric Monoester Hydrolases - antagonists & inhibitors</topic><topic>Potassium Channel Blockers - pharmacology</topic><topic>Protein Kinase C - antagonists & inhibitors</topic><topic>Pyridines - pharmacology</topic><topic>Vaccine</topic><topic>Xenopus laevis</topic><topic>细胞表达</topic><topic>酶抑制剂</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Su, Tzu-rong</creatorcontrib><creatorcontrib>Chen, Cay-huyen</creatorcontrib><creatorcontrib>Huang, Shih-jen</creatorcontrib><creatorcontrib>Lee, Chun-yi</creatorcontrib><creatorcontrib>Su, Mao-chang</creatorcontrib><creatorcontrib>Chen, Gwan-hong</creatorcontrib><creatorcontrib>Li, Shuan-yow</creatorcontrib><creatorcontrib>Yang, 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USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Acta pharmacologica Sinica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Su, Tzu-rong</au><au>Chen, Cay-huyen</au><au>Huang, Shih-jen</au><au>Lee, Chun-yi</au><au>Su, Mao-chang</au><au>Chen, Gwan-hong</au><au>Li, Shuan-yow</au><au>Yang, Jiann-jou</au><au>Lin, Min-jon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional study of the effect of phosphatase inhibitors on KCNQ4 channels expressed in Xenopus oocytes</atitle><jtitle>Acta pharmacologica Sinica</jtitle><stitle>Acta Pharmacol Sin</stitle><addtitle>Acta Pharmacologica Sinica</addtitle><date>2009-09-01</date><risdate>2009</risdate><volume>30</volume><issue>9</issue><spage>1220</spage><epage>1226</epage><pages>1220-1226</pages><issn>1671-4083</issn><eissn>1745-7254</eissn><abstract>Aim： KCNQ4 channels play an important part in adjusting the function of cochlear outer hair cells. The aim of this study was to investigate the effects of ser/thr phosphatase inhibitors on human KCNQ4 channels expressed in Xenopus laevis oocytes. Methods： Synthetic cRNA encoding human KCNQ4 channels was injected into Xenopus oocytes. We used a two-electrode voltage clamp to measure the ion currents in the oocytes. Results： Wild-type KCNQ4 expressed in Xenopus oocytes showed the typical properties of slow activation kinetics and low threshold activation. The outward K~ current was almost completely blocked by a KCNQ4 blocker, linopirdine （0.25 mmol/L）. BIMI （a PKC inhibitor） prevented the effects of PMA （a PKC activator） on the KCNQ4 current, indicating that PKC may be involved in the regulation of KCNQ4 expressed in the Xenopus oocyte system. Treatment with the ser/thr phosphatase inhibitors, cyclosporine （2 pmol/L）, calyculin A （2 pmol/L） or okadaic acid （1 pmol/L）, caused a significant positive shift in V1/2 and a decrease in the conductance of KCNQ4 channels. The V1/2 was shifted from -14.6±0.5 to -6.4±0.4 mV by cyclosporine, -18.8±0.5 to -9.2_＋0.4 mV by calyculin A, and -14.1±0.5 to -0.7＋0.6 mV by okadaic acid. Moreover, the effects of these phosphatase inhibitors （okadaic acid or calyculin A） on the induction of a positive shift of V1/2 were augmented by further addition of PMA. Conclusion： These results indicate that ser/thr phosphatase inhibitors can induce a shift to more positive potentials of the activation curve of the KCNQ4 current. It is highly likely that the phosphatase functions to balance the phosphorylated state of substrate protein and thus has an important role in the regulation of human KCNQ4 channels expressed in Xenopus oocytes.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>19701239</pmid><doi>10.1038/aps.2009.117</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Action Potentials - drug effects Animals Biomedical and Life Sciences Biomedicine Cyclosporine - pharmacology Humans Immunology Indoles - pharmacology Internal Medicine KCNQ Potassium Channels - drug effects Maleimides - pharmacology Medical Microbiology Okadaic Acid - pharmacology Oocytes - metabolism Original original-article Oxazoles - pharmacology Pharmacology/Toxicology Phosphoprotein Phosphatases - antagonists & inhibitors Phosphoric Monoester Hydrolases - antagonists & inhibitors Potassium Channel Blockers - pharmacology Protein Kinase C - antagonists & inhibitors Pyridines - pharmacology Vaccine Xenopus laevis 细胞表达 酶抑制剂 |
| title | Functional study of the effect of phosphatase inhibitors on KCNQ4 channels expressed in Xenopus oocytes |
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