miR-448 regulates potassium voltage-gated channel subfamily A member 4 (KCNA4) in ischemia and heart failure
MicroRNA miR-448 mediates some of the effects of ischemia on arrhythmic risk. Potassium voltage-gated channel subfamily A member 4 (KCNA4) encodes a Kv1.4 current that opens in response to membrane depolarization and is essential for regulating the action potential duration in heart. KCNA4 has a miR...
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| Veröffentlicht in: | Heart rhythm 2023-05, Vol.20 (5), p.730-736 |
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| creator | Kang, Gyeoung-Jin Xie, An Kim, Eunji Dudley, Samuel C. |
| description | MicroRNA miR-448 mediates some of the effects of ischemia on arrhythmic risk. Potassium voltage-gated channel subfamily A member 4 (KCNA4) encodes a Kv1.4 current that opens in response to membrane depolarization and is essential for regulating the action potential duration in heart. KCNA4 has a miR-448 binding site.
We investigated whether miR-448 was involved in the regulation of KCNA4 messenger RNA expression in ischemia.
Quantitative real-time reverse-transcriptase polymerase chain reaction was used to investigate the expression of KCNA4 and miR-448. Pull-down assays were used to examine the interaction between miR-448 and KCNA4. miR-448 decoy and binding site mutation were used to examine the specificity of the effect for KCNA4.
The expression of KCNA4 is diminished in ischemia and human heart failure tissues with ventricular tachycardia. Previously, we have shown that miR-448 is upregulated in ischemia and inhibition can prevent arrhythmic risk after myocardial infarction. The 3ʹ-untranslated region of KCNA4 has a conserved miR-448 binding site. miR-448 bound to this site directly and reduced KCNA4 expression and the transient outward potassium current. Inhibition of miR-448 restored KCNA4.
These findings showed a link between Kv1.4 downregulation and miR-448–mediated upregulation in ischemia, suggesting a new mechanism for the antiarrhythmic effect of miR-448 inhibition. |
| doi_str_mv | 10.1016/j.hrthm.2023.01.021 |
| format | Article |
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We investigated whether miR-448 was involved in the regulation of KCNA4 messenger RNA expression in ischemia.
Quantitative real-time reverse-transcriptase polymerase chain reaction was used to investigate the expression of KCNA4 and miR-448. Pull-down assays were used to examine the interaction between miR-448 and KCNA4. miR-448 decoy and binding site mutation were used to examine the specificity of the effect for KCNA4.
The expression of KCNA4 is diminished in ischemia and human heart failure tissues with ventricular tachycardia. Previously, we have shown that miR-448 is upregulated in ischemia and inhibition can prevent arrhythmic risk after myocardial infarction. The 3ʹ-untranslated region of KCNA4 has a conserved miR-448 binding site. miR-448 bound to this site directly and reduced KCNA4 expression and the transient outward potassium current. Inhibition of miR-448 restored KCNA4.
These findings showed a link between Kv1.4 downregulation and miR-448–mediated upregulation in ischemia, suggesting a new mechanism for the antiarrhythmic effect of miR-448 inhibition.</description><identifier>ISSN: 1547-5271</identifier><identifier>EISSN: 1556-3871</identifier><identifier>DOI: 10.1016/j.hrthm.2023.01.021</identifier><identifier>PMID: 36693615</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Arrhythmias ; Cardiology ; Down-Regulation ; Heart Failure - genetics ; Humans ; Hypoxia ; Ischemia - metabolism ; Kv1.4 Potassium Channel - metabolism ; MicroRNAs - genetics ; miR ; Myocardial Infarction - metabolism ; Potassium - metabolism ; Potassium channels</subject><ispartof>Heart rhythm, 2023-05, Vol.20 (5), p.730-736</ispartof><rights>2023 Heart Rhythm Society</rights><rights>Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-c2678f746f79656baa8d0008054882a64818b65ac9084644cc9888819e9d8aaf3</citedby><cites>FETCH-LOGICAL-c415t-c2678f746f79656baa8d0008054882a64818b65ac9084644cc9888819e9d8aaf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1547527123001030$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36693615$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kang, Gyeoung-Jin</creatorcontrib><creatorcontrib>Xie, An</creatorcontrib><creatorcontrib>Kim, Eunji</creatorcontrib><creatorcontrib>Dudley, Samuel C.</creatorcontrib><title>miR-448 regulates potassium voltage-gated channel subfamily A member 4 (KCNA4) in ischemia and heart failure</title><title>Heart rhythm</title><addtitle>Heart Rhythm</addtitle><description>MicroRNA miR-448 mediates some of the effects of ischemia on arrhythmic risk. Potassium voltage-gated channel subfamily A member 4 (KCNA4) encodes a Kv1.4 current that opens in response to membrane depolarization and is essential for regulating the action potential duration in heart. KCNA4 has a miR-448 binding site.
We investigated whether miR-448 was involved in the regulation of KCNA4 messenger RNA expression in ischemia.
Quantitative real-time reverse-transcriptase polymerase chain reaction was used to investigate the expression of KCNA4 and miR-448. Pull-down assays were used to examine the interaction between miR-448 and KCNA4. miR-448 decoy and binding site mutation were used to examine the specificity of the effect for KCNA4.
The expression of KCNA4 is diminished in ischemia and human heart failure tissues with ventricular tachycardia. Previously, we have shown that miR-448 is upregulated in ischemia and inhibition can prevent arrhythmic risk after myocardial infarction. The 3ʹ-untranslated region of KCNA4 has a conserved miR-448 binding site. miR-448 bound to this site directly and reduced KCNA4 expression and the transient outward potassium current. Inhibition of miR-448 restored KCNA4.
These findings showed a link between Kv1.4 downregulation and miR-448–mediated upregulation in ischemia, suggesting a new mechanism for the antiarrhythmic effect of miR-448 inhibition.</description><subject>Arrhythmias</subject><subject>Cardiology</subject><subject>Down-Regulation</subject><subject>Heart Failure - genetics</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Ischemia - metabolism</subject><subject>Kv1.4 Potassium Channel - metabolism</subject><subject>MicroRNAs - genetics</subject><subject>miR</subject><subject>Myocardial Infarction - metabolism</subject><subject>Potassium - metabolism</subject><subject>Potassium channels</subject><issn>1547-5271</issn><issn>1556-3871</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UU2P1DAMjRCIXRZ-ARLKcffQkrRJmhwQGo34EiuQEJwjN3WnGSXtkLQj7b-nwywruOCLLfv5-eMR8pKzkjOuXu_LIc1DLCtW1SXjJav4I3LJpVRFrRv--BSLppBVwy_Is5z3jFVGsfopuaiVMrXi8pKE6L8VQmiacLcEmDHTwzRDzn6J9DiFGXZY7NZ8R90A44iB5qXtIfpwRzc0YmwxUUGvP2-_bMQN9SP12Q0YPVAYOzogpJn24MOS8Dl50kPI-OLeX5Ef7999334sbr9--LTd3BZOcDkXrlKN7huh-sYoqVoA3THGNJNC6wqU0Fy3SoIzTAslhHNGr8YNmk4D9PUVeXvmPSxtxM7hOCcI9pB8hHRnJ_D238roB7ubjnb9qzBSy5Xh-p4hTT8XzLON61kYAow4LdlWjTLSMClP0PoMdWnKOWH_MIezE6Gye_tbKHsSyjJuV6HWrld_r_jQ80eZFfDmDMD1UUePyWbncXTY-YRutt3k_zvgF9NtpNg</recordid><startdate>20230501</startdate><enddate>20230501</enddate><creator>Kang, Gyeoung-Jin</creator><creator>Xie, An</creator><creator>Kim, Eunji</creator><creator>Dudley, Samuel C.</creator><general>Elsevier Inc</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>20230501</creationdate><title>miR-448 regulates potassium voltage-gated channel subfamily A member 4 (KCNA4) in ischemia and heart failure</title><author>Kang, Gyeoung-Jin ; Xie, An ; Kim, Eunji ; Dudley, Samuel C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-c2678f746f79656baa8d0008054882a64818b65ac9084644cc9888819e9d8aaf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Arrhythmias</topic><topic>Cardiology</topic><topic>Down-Regulation</topic><topic>Heart Failure - genetics</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Ischemia - metabolism</topic><topic>Kv1.4 Potassium Channel - metabolism</topic><topic>MicroRNAs - genetics</topic><topic>miR</topic><topic>Myocardial Infarction - metabolism</topic><topic>Potassium - metabolism</topic><topic>Potassium channels</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kang, Gyeoung-Jin</creatorcontrib><creatorcontrib>Xie, An</creatorcontrib><creatorcontrib>Kim, Eunji</creatorcontrib><creatorcontrib>Dudley, Samuel C.</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>Heart rhythm</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kang, Gyeoung-Jin</au><au>Xie, An</au><au>Kim, Eunji</au><au>Dudley, Samuel C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miR-448 regulates potassium voltage-gated channel subfamily A member 4 (KCNA4) in ischemia and heart failure</atitle><jtitle>Heart rhythm</jtitle><addtitle>Heart Rhythm</addtitle><date>2023-05-01</date><risdate>2023</risdate><volume>20</volume><issue>5</issue><spage>730</spage><epage>736</epage><pages>730-736</pages><issn>1547-5271</issn><eissn>1556-3871</eissn><abstract>MicroRNA miR-448 mediates some of the effects of ischemia on arrhythmic risk. Potassium voltage-gated channel subfamily A member 4 (KCNA4) encodes a Kv1.4 current that opens in response to membrane depolarization and is essential for regulating the action potential duration in heart. KCNA4 has a miR-448 binding site.
We investigated whether miR-448 was involved in the regulation of KCNA4 messenger RNA expression in ischemia.
Quantitative real-time reverse-transcriptase polymerase chain reaction was used to investigate the expression of KCNA4 and miR-448. Pull-down assays were used to examine the interaction between miR-448 and KCNA4. miR-448 decoy and binding site mutation were used to examine the specificity of the effect for KCNA4.
The expression of KCNA4 is diminished in ischemia and human heart failure tissues with ventricular tachycardia. Previously, we have shown that miR-448 is upregulated in ischemia and inhibition can prevent arrhythmic risk after myocardial infarction. The 3ʹ-untranslated region of KCNA4 has a conserved miR-448 binding site. miR-448 bound to this site directly and reduced KCNA4 expression and the transient outward potassium current. Inhibition of miR-448 restored KCNA4.
These findings showed a link between Kv1.4 downregulation and miR-448–mediated upregulation in ischemia, suggesting a new mechanism for the antiarrhythmic effect of miR-448 inhibition.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>36693615</pmid><doi>10.1016/j.hrthm.2023.01.021</doi><tpages>7</tpages></addata></record> |
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| ispartof | Heart rhythm, 2023-05, Vol.20 (5), p.730-736 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Arrhythmias Cardiology Down-Regulation Heart Failure - genetics Humans Hypoxia Ischemia - metabolism Kv1.4 Potassium Channel - metabolism MicroRNAs - genetics miR Myocardial Infarction - metabolism Potassium - metabolism Potassium channels |
| title | miR-448 regulates potassium voltage-gated channel subfamily A member 4 (KCNA4) in ischemia and heart failure |
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