The ICl,swell inhibitor DCPIB blocks Kir channels that possess weak affinity for PIP2
Inwardly rectifying K + (Kir) channels are important contributors to the resting membrane potential and regulate cellular excitability. The activity of Kir channels depends critically on the phospholipid PIP 2 . Several modulators of the activity of Kir channels alter the apparent affinity of the ch...
Gespeichert in:
| Veröffentlicht in: | Pflügers Archiv 2016-05, Vol.468 (5), p.817-824 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 824 |
|---|---|
| container_issue | 5 |
| container_start_page | 817 |
| container_title | Pflügers Archiv |
| container_volume | 468 |
| creator | Deng, Wu Mahajan, Rahul Baumgarten, Clive M. Logothetis, Diomedes E. |
| description | Inwardly rectifying K
+
(Kir) channels are important contributors to the resting membrane potential and regulate cellular excitability. The activity of Kir channels depends critically on the phospholipid PIP
2
. Several modulators of the activity of Kir channels alter the apparent affinity of the channel to PIP
2
. Channels with high apparent affinity to PIP
2
may not respond to a given modulator, but mutations that decrease such affinity can render the channel susceptible to modulation. Here, we identify a known inhibitor of the swelling-activated Cl
−
current, DCPIB, as an effective inhibitor of a number of Kir channels both in native cardiac cells and in heterologous expression systems. We show that the apparent affinity to PIP
2
determines whether DCPIB will serve as an efficient blocker of Kir channels. These effects are consistent with a model in which DCPIB competes with PIP
2
for a common binding site. |
| doi_str_mv | 10.1007/s00424-016-1794-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5317042</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1784461193</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3579-b998943a90ce5d005154f945a581f8b0a5de1ccaed7238cefc0aeba1672e880b3</originalsourceid><addsrcrecordid>eNp9UU1P3DAQtVBR2dL-AC6Vjz007fgjsX2pRJe2rEBiD3C2HO-EGLLOYmdB_PsaLUX0wmkO72Nm3iPkiME3BqC-ZwDJZQWsqZgysjJ7ZMak4BUHJt6RGYBgVaMafUA-5HwDAFxq_p4c8EYLpbWekavLHuliPnzNDzgMNMQ-tGEaEz2ZLxc_aTuM_jbTs5Co712MOGQ69W6imzFnzJk-oLulrutCDNMj7YpwuVjyj2S_c0PGT8_zkFz9_nU5P63OL_4s5sfnlRe1MlVrjDZSOAMe6xVAzWrZGVm7WrNOt-DqFTLvHa4UF9pj58Fh61ijOGoNrTgkP3a-m227xpXHOCU32E0Ka5ce7eiC_R-JobfX472tBVMlu2Lw5dkgjXdbzJNdh-xLEi7iuM2WKS1lw5gRhcp2VJ_K7wm7lzUM7FMddleHLXXYpzqsKZrPr-97UfzLvxD4jpALFK8x2Ztxm2LJ7A3Xv3bflcw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1784461193</pqid></control><display><type>article</type><title>The ICl,swell inhibitor DCPIB blocks Kir channels that possess weak affinity for PIP2</title><source>MEDLINE</source><source>SpringerLink Journals (MCLS)</source><creator>Deng, Wu ; Mahajan, Rahul ; Baumgarten, Clive M. ; Logothetis, Diomedes E.</creator><creatorcontrib>Deng, Wu ; Mahajan, Rahul ; Baumgarten, Clive M. ; Logothetis, Diomedes E.</creatorcontrib><description>Inwardly rectifying K
+
(Kir) channels are important contributors to the resting membrane potential and regulate cellular excitability. The activity of Kir channels depends critically on the phospholipid PIP
2
. Several modulators of the activity of Kir channels alter the apparent affinity of the channel to PIP
2
. Channels with high apparent affinity to PIP
2
may not respond to a given modulator, but mutations that decrease such affinity can render the channel susceptible to modulation. Here, we identify a known inhibitor of the swelling-activated Cl
−
current, DCPIB, as an effective inhibitor of a number of Kir channels both in native cardiac cells and in heterologous expression systems. We show that the apparent affinity to PIP
2
determines whether DCPIB will serve as an efficient blocker of Kir channels. These effects are consistent with a model in which DCPIB competes with PIP
2
for a common binding site.</description><identifier>ISSN: 0031-6768</identifier><identifier>EISSN: 1432-2013</identifier><identifier>DOI: 10.1007/s00424-016-1794-9</identifier><identifier>PMID: 26837888</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Action Potentials - drug effects ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Cell Biology ; Cell Size - drug effects ; Cells, Cultured ; Chloride Channels - antagonists & inhibitors ; Chloride Channels - metabolism ; Cyclopentanes - pharmacology ; Human Physiology ; Indans - pharmacology ; Ion Channels ; Molecular Medicine ; Myocytes, Cardiac - drug effects ; Myocytes, Cardiac - metabolism ; Myocytes, Cardiac - physiology ; Neurosciences ; Phosphatidylinositol 4,5-Diphosphate - metabolism ; Potassium Channels, Inwardly Rectifying - antagonists & inhibitors ; Potassium Channels, Inwardly Rectifying - drug effects ; Rabbits ; Receptors ; Receptors and Transporters ; Xenopus</subject><ispartof>Pflügers Archiv, 2016-05, Vol.468 (5), p.817-824</ispartof><rights>Springer-Verlag Berlin Heidelberg 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3579-b998943a90ce5d005154f945a581f8b0a5de1ccaed7238cefc0aeba1672e880b3</citedby><cites>FETCH-LOGICAL-c3579-b998943a90ce5d005154f945a581f8b0a5de1ccaed7238cefc0aeba1672e880b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00424-016-1794-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00424-016-1794-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26837888$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Deng, Wu</creatorcontrib><creatorcontrib>Mahajan, Rahul</creatorcontrib><creatorcontrib>Baumgarten, Clive M.</creatorcontrib><creatorcontrib>Logothetis, Diomedes E.</creatorcontrib><title>The ICl,swell inhibitor DCPIB blocks Kir channels that possess weak affinity for PIP2</title><title>Pflügers Archiv</title><addtitle>Pflugers Arch - Eur J Physiol</addtitle><addtitle>Pflugers Arch</addtitle><description>Inwardly rectifying K
+
(Kir) channels are important contributors to the resting membrane potential and regulate cellular excitability. The activity of Kir channels depends critically on the phospholipid PIP
2
. Several modulators of the activity of Kir channels alter the apparent affinity of the channel to PIP
2
. Channels with high apparent affinity to PIP
2
may not respond to a given modulator, but mutations that decrease such affinity can render the channel susceptible to modulation. Here, we identify a known inhibitor of the swelling-activated Cl
−
current, DCPIB, as an effective inhibitor of a number of Kir channels both in native cardiac cells and in heterologous expression systems. We show that the apparent affinity to PIP
2
determines whether DCPIB will serve as an efficient blocker of Kir channels. These effects are consistent with a model in which DCPIB competes with PIP
2
for a common binding site.</description><subject>Action Potentials - drug effects</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell Biology</subject><subject>Cell Size - drug effects</subject><subject>Cells, Cultured</subject><subject>Chloride Channels - antagonists & inhibitors</subject><subject>Chloride Channels - metabolism</subject><subject>Cyclopentanes - pharmacology</subject><subject>Human Physiology</subject><subject>Indans - pharmacology</subject><subject>Ion Channels</subject><subject>Molecular Medicine</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Myocytes, Cardiac - physiology</subject><subject>Neurosciences</subject><subject>Phosphatidylinositol 4,5-Diphosphate - metabolism</subject><subject>Potassium Channels, Inwardly Rectifying - antagonists & inhibitors</subject><subject>Potassium Channels, Inwardly Rectifying - drug effects</subject><subject>Rabbits</subject><subject>Receptors</subject><subject>Receptors and Transporters</subject><subject>Xenopus</subject><issn>0031-6768</issn><issn>1432-2013</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU1P3DAQtVBR2dL-AC6Vjz007fgjsX2pRJe2rEBiD3C2HO-EGLLOYmdB_PsaLUX0wmkO72Nm3iPkiME3BqC-ZwDJZQWsqZgysjJ7ZMak4BUHJt6RGYBgVaMafUA-5HwDAFxq_p4c8EYLpbWekavLHuliPnzNDzgMNMQ-tGEaEz2ZLxc_aTuM_jbTs5Co712MOGQ69W6imzFnzJk-oLulrutCDNMj7YpwuVjyj2S_c0PGT8_zkFz9_nU5P63OL_4s5sfnlRe1MlVrjDZSOAMe6xVAzWrZGVm7WrNOt-DqFTLvHa4UF9pj58Fh61ijOGoNrTgkP3a-m227xpXHOCU32E0Ka5ce7eiC_R-JobfX472tBVMlu2Lw5dkgjXdbzJNdh-xLEi7iuM2WKS1lw5gRhcp2VJ_K7wm7lzUM7FMddleHLXXYpzqsKZrPr-97UfzLvxD4jpALFK8x2Ztxm2LJ7A3Xv3bflcw</recordid><startdate>20160501</startdate><enddate>20160501</enddate><creator>Deng, Wu</creator><creator>Mahajan, Rahul</creator><creator>Baumgarten, Clive M.</creator><creator>Logothetis, Diomedes E.</creator><general>Springer Berlin Heidelberg</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160501</creationdate><title>The ICl,swell inhibitor DCPIB blocks Kir channels that possess weak affinity for PIP2</title><author>Deng, Wu ; Mahajan, Rahul ; Baumgarten, Clive M. ; Logothetis, Diomedes E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3579-b998943a90ce5d005154f945a581f8b0a5de1ccaed7238cefc0aeba1672e880b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Action Potentials - drug effects</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell Biology</topic><topic>Cell Size - drug effects</topic><topic>Cells, Cultured</topic><topic>Chloride Channels - antagonists & inhibitors</topic><topic>Chloride Channels - metabolism</topic><topic>Cyclopentanes - pharmacology</topic><topic>Human Physiology</topic><topic>Indans - pharmacology</topic><topic>Ion Channels</topic><topic>Molecular Medicine</topic><topic>Myocytes, Cardiac - drug effects</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Myocytes, Cardiac - physiology</topic><topic>Neurosciences</topic><topic>Phosphatidylinositol 4,5-Diphosphate - metabolism</topic><topic>Potassium Channels, Inwardly Rectifying - antagonists & inhibitors</topic><topic>Potassium Channels, Inwardly Rectifying - drug effects</topic><topic>Rabbits</topic><topic>Receptors</topic><topic>Receptors and Transporters</topic><topic>Xenopus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Deng, Wu</creatorcontrib><creatorcontrib>Mahajan, Rahul</creatorcontrib><creatorcontrib>Baumgarten, Clive M.</creatorcontrib><creatorcontrib>Logothetis, Diomedes E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Pflügers Archiv</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Deng, Wu</au><au>Mahajan, Rahul</au><au>Baumgarten, Clive M.</au><au>Logothetis, Diomedes E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The ICl,swell inhibitor DCPIB blocks Kir channels that possess weak affinity for PIP2</atitle><jtitle>Pflügers Archiv</jtitle><stitle>Pflugers Arch - Eur J Physiol</stitle><addtitle>Pflugers Arch</addtitle><date>2016-05-01</date><risdate>2016</risdate><volume>468</volume><issue>5</issue><spage>817</spage><epage>824</epage><pages>817-824</pages><issn>0031-6768</issn><eissn>1432-2013</eissn><abstract>Inwardly rectifying K
+
(Kir) channels are important contributors to the resting membrane potential and regulate cellular excitability. The activity of Kir channels depends critically on the phospholipid PIP
2
. Several modulators of the activity of Kir channels alter the apparent affinity of the channel to PIP
2
. Channels with high apparent affinity to PIP
2
may not respond to a given modulator, but mutations that decrease such affinity can render the channel susceptible to modulation. Here, we identify a known inhibitor of the swelling-activated Cl
−
current, DCPIB, as an effective inhibitor of a number of Kir channels both in native cardiac cells and in heterologous expression systems. We show that the apparent affinity to PIP
2
determines whether DCPIB will serve as an efficient blocker of Kir channels. These effects are consistent with a model in which DCPIB competes with PIP
2
for a common binding site.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>26837888</pmid><doi>10.1007/s00424-016-1794-9</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0031-6768 |
| ispartof | Pflügers Archiv, 2016-05, Vol.468 (5), p.817-824 |
| issn | 0031-6768 1432-2013 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5317042 |
| source | MEDLINE; SpringerLink Journals (MCLS) |
| subjects | Action Potentials - drug effects Animals Biomedical and Life Sciences Biomedicine Cell Biology Cell Size - drug effects Cells, Cultured Chloride Channels - antagonists & inhibitors Chloride Channels - metabolism Cyclopentanes - pharmacology Human Physiology Indans - pharmacology Ion Channels Molecular Medicine Myocytes, Cardiac - drug effects Myocytes, Cardiac - metabolism Myocytes, Cardiac - physiology Neurosciences Phosphatidylinositol 4,5-Diphosphate - metabolism Potassium Channels, Inwardly Rectifying - antagonists & inhibitors Potassium Channels, Inwardly Rectifying - drug effects Rabbits Receptors Receptors and Transporters Xenopus |
| title | The ICl,swell inhibitor DCPIB blocks Kir channels that possess weak affinity for PIP2 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T22%3A27%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20ICl,swell%20inhibitor%20DCPIB%20blocks%20Kir%20channels%20that%20possess%20weak%20affinity%20for%20PIP2&rft.jtitle=Pfl%C3%BCgers%20Archiv&rft.au=Deng,%20Wu&rft.date=2016-05-01&rft.volume=468&rft.issue=5&rft.spage=817&rft.epage=824&rft.pages=817-824&rft.issn=0031-6768&rft.eissn=1432-2013&rft_id=info:doi/10.1007/s00424-016-1794-9&rft_dat=%3Cproquest_pubme%3E1784461193%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1784461193&rft_id=info:pmid/26837888&rfr_iscdi=true |