Activation of Inward Rectifier K+ Channel 2.1 by PDGF-BB in Rat Vascular Smooth Muscle Cells through Protein Kinase A
Platelet-derived growth factor-BB (PDGF-BB) can induce the proliferation, migration, and phenotypic modulation of vascular smooth muscle cells (VSMCs). We used patch clamp methods to study the effects of PDGF-BB on inward rectifier K+ channel 2.1 (Kir2.1) channels in rat thoracic aorta VSMCs (RASMCs...
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| creator | Qiao, Yong Liu, Bo Yan, Gaoliang Luo, Erfei Wang, Dong Tang, Chengchun Hou, Jiantong |
| description | Platelet-derived growth factor-BB (PDGF-BB) can induce the proliferation, migration, and phenotypic modulation of vascular smooth muscle cells (VSMCs). We used patch clamp methods to study the effects of PDGF-BB on inward rectifier K+ channel 2.1 (Kir2.1) channels in rat thoracic aorta VSMCs (RASMCs). PDGF-BB (25 ng/mL) increased Kir2.x currents (−11.81±2.47 pA/pF, P |
| doi_str_mv | 10.1155/2020/4370832 |
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We used patch clamp methods to study the effects of PDGF-BB on inward rectifier K+ channel 2.1 (Kir2.1) channels in rat thoracic aorta VSMCs (RASMCs). PDGF-BB (25 ng/mL) increased Kir2.x currents (−11.81±2.47 pA/pF, P<0.05 vs. CON, n=10). Ba2+(50 μM) decreased Kir2.x currents (−2.13±0.23 pA/pF, P<0.05 vs. CON, n=10), which were promoted by PDGF-BB (−6.98±1.03 pA/pF). PDGF-BB specifically activates Kir2.1 but not Kir2.2 and Kir2.3 channels in HEK-293 cells. The PDGF-BB-induced stimulation of Kir2.1 currents was blocked by the PDGF-BB receptor β (PDGF-BBRβ) inhibitor AG1295 and was not affected by the PDGF-BBRα inhibitor AG1296. The PDGF-BB-induced stimulation of Kir2.1 currents was blocked by the protein kinase A inhibitor Rp-8-CPT-cAMPs; however, the antagonist of protein kinase B (GSK690693) had marginal effects on current activity. The PDGF-BB-induced stimulation of Kir2.1 currents was enhanced by forskolin, an adenylyl cyclase (AC) activator, and was blocked by the AC inhibitor SQ22536. We conclude that PDGF-BB increases Kir2.1 currents via PDGF-BBRβ through activation of cAMP-PKA signaling in RASMCs.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2020/4370832</identifier><identifier>PMID: 32461988</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Activation ; Adenosine ; Adenylate cyclase ; AKT protein ; Animals ; Aorta ; Aorta, Thoracic - cytology ; Becaplermin - pharmacology ; Cell proliferation ; Cells, Cultured ; Channels ; Colforsin - pharmacology ; Coronary vessels ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Enzyme inhibitors ; Forskolin ; Gene expression ; Genotype & phenotype ; Growth factors ; HEK293 Cells ; Humans ; Kinases ; Laboratory animals ; Male ; Muscle, Smooth, Vascular - cytology ; Muscles ; Platelet-derived growth factor ; Platelet-derived growth factor BB ; Potassium channels ; Potassium channels (inwardly-rectifying) ; Potassium Channels, Inwardly Rectifying - drug effects ; Potassium Channels, Inwardly Rectifying - metabolism ; Protein kinase A ; Protein kinase A inhibitors ; Proteins ; Rats ; Rats, Sprague-Dawley ; Rectifiers ; Rodents ; Signal Transduction - drug effects ; Smooth muscle ; Stimulation ; Thermal cycling ; Thorax</subject><ispartof>BioMed research international, 2020, Vol.2020 (2020), p.1-9</ispartof><rights>Copyright © 2020 Chengchun Tang et al.</rights><rights>Copyright © 2020 Chengchun Tang et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. http://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2020 Chengchun Tang et al. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c537t-8d650af8cceb7a05353597d5cf426b5cb24ea97b3ac1d0794decb5e2909f32043</citedby><cites>FETCH-LOGICAL-c537t-8d650af8cceb7a05353597d5cf426b5cb24ea97b3ac1d0794decb5e2909f32043</cites><orcidid>0000-0003-3767-3551 ; 0000-0003-2563-167X ; 0000-0002-7666-7309 ; 0000-0003-1063-8967</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212311/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212311/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,4010,27902,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32461988$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Schatten, Heide</contributor><contributor>Heide Schatten</contributor><creatorcontrib>Qiao, Yong</creatorcontrib><creatorcontrib>Liu, Bo</creatorcontrib><creatorcontrib>Yan, Gaoliang</creatorcontrib><creatorcontrib>Luo, Erfei</creatorcontrib><creatorcontrib>Wang, Dong</creatorcontrib><creatorcontrib>Tang, Chengchun</creatorcontrib><creatorcontrib>Hou, Jiantong</creatorcontrib><title>Activation of Inward Rectifier K+ Channel 2.1 by PDGF-BB in Rat Vascular Smooth Muscle Cells through Protein Kinase A</title><title>BioMed research international</title><addtitle>Biomed Res Int</addtitle><description>Platelet-derived growth factor-BB (PDGF-BB) can induce the proliferation, migration, and phenotypic modulation of vascular smooth muscle cells (VSMCs). We used patch clamp methods to study the effects of PDGF-BB on inward rectifier K+ channel 2.1 (Kir2.1) channels in rat thoracic aorta VSMCs (RASMCs). PDGF-BB (25 ng/mL) increased Kir2.x currents (−11.81±2.47 pA/pF, P<0.05 vs. CON, n=10). Ba2+(50 μM) decreased Kir2.x currents (−2.13±0.23 pA/pF, P<0.05 vs. CON, n=10), which were promoted by PDGF-BB (−6.98±1.03 pA/pF). PDGF-BB specifically activates Kir2.1 but not Kir2.2 and Kir2.3 channels in HEK-293 cells. The PDGF-BB-induced stimulation of Kir2.1 currents was blocked by the PDGF-BB receptor β (PDGF-BBRβ) inhibitor AG1295 and was not affected by the PDGF-BBRα inhibitor AG1296. The PDGF-BB-induced stimulation of Kir2.1 currents was blocked by the protein kinase A inhibitor Rp-8-CPT-cAMPs; however, the antagonist of protein kinase B (GSK690693) had marginal effects on current activity. The PDGF-BB-induced stimulation of Kir2.1 currents was enhanced by forskolin, an adenylyl cyclase (AC) activator, and was blocked by the AC inhibitor SQ22536. We conclude that PDGF-BB increases Kir2.1 currents via PDGF-BBRβ through activation of cAMP-PKA signaling in RASMCs.</description><subject>Activation</subject><subject>Adenosine</subject><subject>Adenylate cyclase</subject><subject>AKT protein</subject><subject>Animals</subject><subject>Aorta</subject><subject>Aorta, Thoracic - cytology</subject><subject>Becaplermin - pharmacology</subject><subject>Cell proliferation</subject><subject>Cells, Cultured</subject><subject>Channels</subject><subject>Colforsin - pharmacology</subject><subject>Coronary vessels</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>Enzyme inhibitors</subject><subject>Forskolin</subject><subject>Gene expression</subject><subject>Genotype & phenotype</subject><subject>Growth factors</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Kinases</subject><subject>Laboratory animals</subject><subject>Male</subject><subject>Muscle, Smooth, Vascular - cytology</subject><subject>Muscles</subject><subject>Platelet-derived growth factor</subject><subject>Platelet-derived growth factor BB</subject><subject>Potassium channels</subject><subject>Potassium channels (inwardly-rectifying)</subject><subject>Potassium Channels, Inwardly Rectifying - drug effects</subject><subject>Potassium Channels, Inwardly Rectifying - metabolism</subject><subject>Protein kinase A</subject><subject>Protein kinase A inhibitors</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rectifiers</subject><subject>Rodents</subject><subject>Signal Transduction - drug effects</subject><subject>Smooth muscle</subject><subject>Stimulation</subject><subject>Thermal cycling</subject><subject>Thorax</subject><issn>2314-6133</issn><issn>2314-6141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkktP3DAUhaOqVUGUXdeVpW4q0YCfcbKpNEzLQ4BA0HZrOc4NMcrY1HZA_Hs8mun0scJe2LK_e-Rzj4viPcH7hAhxQDHFB5xJXDP6qtimjPCyIpy83uwZ2yp2Y7zDedSkwk31tthilFekqevtYpqZZB90st4h36NT96hDh64hn_YWAjrbQ_NBOwcjovsEtU_o6uvxUXl4iKxD1zqhnzqaadQB3Sy8TwO6mKIZAc1hHCNKQ_DT7YCugk-QC86s0xHQ7F3xptdjhN31ulP8OPr2fX5Snl8en85n56URTKay7iqBdV8bA63UWLA8G9kJ03NatcK0lINuZMu0IR2WDe_AtAJog5ueUczZTvFlpXs_tQvoDLgU9Kjug13o8KS8turfG2cHdesflKQk949kgU9rgeB_TRCTWthosjftwE9RUY6lkE0l6ox-_A-981Nw2d6SwlRyiZeCn1eUCT7GAP3mMQSrZaRqGalaR5rxD38b2MC_A8zA3goYrOv0o32hHGQGev2Hzv8kd409A92FsKc</recordid><startdate>2020</startdate><enddate>2020</enddate><creator>Qiao, Yong</creator><creator>Liu, Bo</creator><creator>Yan, Gaoliang</creator><creator>Luo, Erfei</creator><creator>Wang, Dong</creator><creator>Tang, Chengchun</creator><creator>Hou, Jiantong</creator><general>Hindawi Publishing Corporation</general><general>Hindawi</general><general>Hindawi Limited</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><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>3V.</scope><scope>7QL</scope><scope>7QO</scope><scope>7T7</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>CWDGH</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3767-3551</orcidid><orcidid>https://orcid.org/0000-0003-2563-167X</orcidid><orcidid>https://orcid.org/0000-0002-7666-7309</orcidid><orcidid>https://orcid.org/0000-0003-1063-8967</orcidid></search><sort><creationdate>2020</creationdate><title>Activation of Inward Rectifier K+ Channel 2.1 by PDGF-BB in Rat Vascular Smooth Muscle Cells through Protein Kinase A</title><author>Qiao, Yong ; Liu, Bo ; Yan, Gaoliang ; Luo, Erfei ; Wang, Dong ; Tang, Chengchun ; Hou, Jiantong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c537t-8d650af8cceb7a05353597d5cf426b5cb24ea97b3ac1d0794decb5e2909f32043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Activation</topic><topic>Adenosine</topic><topic>Adenylate cyclase</topic><topic>AKT protein</topic><topic>Animals</topic><topic>Aorta</topic><topic>Aorta, Thoracic - cytology</topic><topic>Becaplermin - pharmacology</topic><topic>Cell proliferation</topic><topic>Cells, Cultured</topic><topic>Channels</topic><topic>Colforsin - pharmacology</topic><topic>Coronary vessels</topic><topic>Cyclic AMP-Dependent Protein Kinases - metabolism</topic><topic>Enzyme inhibitors</topic><topic>Forskolin</topic><topic>Gene expression</topic><topic>Genotype & phenotype</topic><topic>Growth factors</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Kinases</topic><topic>Laboratory animals</topic><topic>Male</topic><topic>Muscle, Smooth, Vascular - cytology</topic><topic>Muscles</topic><topic>Platelet-derived growth factor</topic><topic>Platelet-derived growth factor BB</topic><topic>Potassium channels</topic><topic>Potassium channels (inwardly-rectifying)</topic><topic>Potassium Channels, Inwardly Rectifying - drug effects</topic><topic>Potassium Channels, Inwardly Rectifying - metabolism</topic><topic>Protein kinase A</topic><topic>Protein kinase A inhibitors</topic><topic>Proteins</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Rectifiers</topic><topic>Rodents</topic><topic>Signal Transduction - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BioMed research international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qiao, Yong</au><au>Liu, Bo</au><au>Yan, Gaoliang</au><au>Luo, Erfei</au><au>Wang, Dong</au><au>Tang, Chengchun</au><au>Hou, Jiantong</au><au>Schatten, Heide</au><au>Heide Schatten</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation of Inward Rectifier K+ Channel 2.1 by PDGF-BB in Rat Vascular Smooth Muscle Cells through Protein Kinase A</atitle><jtitle>BioMed research international</jtitle><addtitle>Biomed Res Int</addtitle><date>2020</date><risdate>2020</risdate><volume>2020</volume><issue>2020</issue><spage>1</spage><epage>9</epage><pages>1-9</pages><issn>2314-6133</issn><eissn>2314-6141</eissn><abstract>Platelet-derived growth factor-BB (PDGF-BB) can induce the proliferation, migration, and phenotypic modulation of vascular smooth muscle cells (VSMCs). We used patch clamp methods to study the effects of PDGF-BB on inward rectifier K+ channel 2.1 (Kir2.1) channels in rat thoracic aorta VSMCs (RASMCs). PDGF-BB (25 ng/mL) increased Kir2.x currents (−11.81±2.47 pA/pF, P<0.05 vs. CON, n=10). Ba2+(50 μM) decreased Kir2.x currents (−2.13±0.23 pA/pF, P<0.05 vs. CON, n=10), which were promoted by PDGF-BB (−6.98±1.03 pA/pF). PDGF-BB specifically activates Kir2.1 but not Kir2.2 and Kir2.3 channels in HEK-293 cells. The PDGF-BB-induced stimulation of Kir2.1 currents was blocked by the PDGF-BB receptor β (PDGF-BBRβ) inhibitor AG1295 and was not affected by the PDGF-BBRα inhibitor AG1296. The PDGF-BB-induced stimulation of Kir2.1 currents was blocked by the protein kinase A inhibitor Rp-8-CPT-cAMPs; however, the antagonist of protein kinase B (GSK690693) had marginal effects on current activity. The PDGF-BB-induced stimulation of Kir2.1 currents was enhanced by forskolin, an adenylyl cyclase (AC) activator, and was blocked by the AC inhibitor SQ22536. We conclude that PDGF-BB increases Kir2.1 currents via PDGF-BBRβ through activation of cAMP-PKA signaling in RASMCs.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>32461988</pmid><doi>10.1155/2020/4370832</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-3767-3551</orcidid><orcidid>https://orcid.org/0000-0003-2563-167X</orcidid><orcidid>https://orcid.org/0000-0002-7666-7309</orcidid><orcidid>https://orcid.org/0000-0003-1063-8967</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Activation Adenosine Adenylate cyclase AKT protein Animals Aorta Aorta, Thoracic - cytology Becaplermin - pharmacology Cell proliferation Cells, Cultured Channels Colforsin - pharmacology Coronary vessels Cyclic AMP-Dependent Protein Kinases - metabolism Enzyme inhibitors Forskolin Gene expression Genotype & phenotype Growth factors HEK293 Cells Humans Kinases Laboratory animals Male Muscle, Smooth, Vascular - cytology Muscles Platelet-derived growth factor Platelet-derived growth factor BB Potassium channels Potassium channels (inwardly-rectifying) Potassium Channels, Inwardly Rectifying - drug effects Potassium Channels, Inwardly Rectifying - metabolism Protein kinase A Protein kinase A inhibitors Proteins Rats Rats, Sprague-Dawley Rectifiers Rodents Signal Transduction - drug effects Smooth muscle Stimulation Thermal cycling Thorax |
| title | Activation of Inward Rectifier K+ Channel 2.1 by PDGF-BB in Rat Vascular Smooth Muscle Cells through Protein Kinase A |
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