Kv4.3 is not required for the generation of functional Ito,f channels in adult mouse ventricles
Abstract Accumulated evidence suggests that the heteromeric assembly of Kv4.2 and Kv4.3 α-subunits underlies the fast transient Kv current ( Ito,f ) in rodent ventricles. Recent studies, however, demonstrated that the targeted deletion of Kv4.2 results in the complete elimination of Ito,f in adult m...
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description | Abstract Accumulated evidence suggests that the heteromeric assembly of Kv4.2 and Kv4.3 α-subunits underlies the fast transient Kv current ( Ito,f ) in rodent ventricles. Recent studies, however, demonstrated that the targeted deletion of Kv4.2 results in the complete elimination of Ito,f in adult mouse ventricles, revealing an essential role for the Kv4.2 α-subunit in the generation of mouse ventricular Ito,f channels. The present study was undertaken to investigate directly the functional role of Kv4.3 by examining the effects of the targeted disruption of the KCND3 (Kv4.3) locus. Mice lacking Kv4.3 (Kv4.3−/−) appear indistinguishable from wild-type control animals, and no structural or functional abnormalities were evident in Kv4.3−/− hearts. Voltage-clamp recordings revealed that functional Ito,f channels are expressed in Kv4.3−/− ventricular myocytes, and that mean Ito,f densities are similar to those recorded from wild-type cells. In addition, Ito,f properties (inactivation rates, voltage dependences of inactivation and rates of recovery from inactivation) in Kv4.3−/− and wild-type mouse ventricular myocytes were indistinguishable. Quantitative RT-PCR and Western blot analyses did not reveal any measurable changes in the expression of Kv4.2 or the Kv channel interacting protein (KChIP2) in Kv4.3−/− ventricles. Taken together, the results presented here suggest that, in contrast with Kv4.2, Kv4.3 is not required for the generation of functional mouse ventricular Ito,f channels. |
doi_str_mv | 10.1016/j.yjmcc.2007.10.007 |
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Recent studies, however, demonstrated that the targeted deletion of Kv4.2 results in the complete elimination of Ito,f in adult mouse ventricles, revealing an essential role for the Kv4.2 α-subunit in the generation of mouse ventricular Ito,f channels. The present study was undertaken to investigate directly the functional role of Kv4.3 by examining the effects of the targeted disruption of the KCND3 (Kv4.3) locus. Mice lacking Kv4.3 (Kv4.3−/−) appear indistinguishable from wild-type control animals, and no structural or functional abnormalities were evident in Kv4.3−/− hearts. Voltage-clamp recordings revealed that functional Ito,f channels are expressed in Kv4.3−/− ventricular myocytes, and that mean Ito,f densities are similar to those recorded from wild-type cells. In addition, Ito,f properties (inactivation rates, voltage dependences of inactivation and rates of recovery from inactivation) in Kv4.3−/− and wild-type mouse ventricular myocytes were indistinguishable. Quantitative RT-PCR and Western blot analyses did not reveal any measurable changes in the expression of Kv4.2 or the Kv channel interacting protein (KChIP2) in Kv4.3−/− ventricles. Taken together, the results presented here suggest that, in contrast with Kv4.2, Kv4.3 is not required for the generation of functional mouse ventricular Ito,f channels.</description><identifier>ISSN: 0022-2828</identifier><identifier>EISSN: 1095-8584</identifier><identifier>DOI: 10.1016/j.yjmcc.2007.10.007</identifier><identifier>PMID: 18045613</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Cardiovascular ; Electrophysiology ; Gene Expression Regulation ; Gene Targeting ; Heart Ventricles - metabolism ; Ion Channel Gating ; Life Sciences ; Mice ; Mice, Inbred C57BL ; Myocytes, Cardiac - metabolism ; Phenotype ; Protein Subunits - genetics ; Protein Subunits - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Shal Potassium Channels - chemistry ; Shal Potassium Channels - genetics ; Shal Potassium Channels - metabolism</subject><ispartof>J Mol Cell Cardiol, 2008-01, Vol.44 (1), p.95-104</ispartof><rights>Elsevier Inc.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4077-cf5f1431e6c69dc55e2d7b5862e393b2fd223e623791994d7240d426288fe723</citedby><cites>FETCH-LOGICAL-c4077-cf5f1431e6c69dc55e2d7b5862e393b2fd223e623791994d7240d426288fe723</cites><orcidid>0000-0003-0962-9756</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18045613$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-02363790$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Niwa, Noriko</creatorcontrib><creatorcontrib>Wang, Wei</creatorcontrib><creatorcontrib>Sha, Qun</creatorcontrib><creatorcontrib>Marionneau, Céline</creatorcontrib><creatorcontrib>Nerbonne, Jeanne M</creatorcontrib><title>Kv4.3 is not required for the generation of functional Ito,f channels in adult mouse ventricles</title><title>J Mol Cell Cardiol</title><addtitle>J Mol Cell Cardiol</addtitle><description>Abstract Accumulated evidence suggests that the heteromeric assembly of Kv4.2 and Kv4.3 α-subunits underlies the fast transient Kv current ( Ito,f ) in rodent ventricles. Recent studies, however, demonstrated that the targeted deletion of Kv4.2 results in the complete elimination of Ito,f in adult mouse ventricles, revealing an essential role for the Kv4.2 α-subunit in the generation of mouse ventricular Ito,f channels. The present study was undertaken to investigate directly the functional role of Kv4.3 by examining the effects of the targeted disruption of the KCND3 (Kv4.3) locus. Mice lacking Kv4.3 (Kv4.3−/−) appear indistinguishable from wild-type control animals, and no structural or functional abnormalities were evident in Kv4.3−/− hearts. Voltage-clamp recordings revealed that functional Ito,f channels are expressed in Kv4.3−/− ventricular myocytes, and that mean Ito,f densities are similar to those recorded from wild-type cells. In addition, Ito,f properties (inactivation rates, voltage dependences of inactivation and rates of recovery from inactivation) in Kv4.3−/− and wild-type mouse ventricular myocytes were indistinguishable. Quantitative RT-PCR and Western blot analyses did not reveal any measurable changes in the expression of Kv4.2 or the Kv channel interacting protein (KChIP2) in Kv4.3−/− ventricles. Taken together, the results presented here suggest that, in contrast with Kv4.2, Kv4.3 is not required for the generation of functional mouse ventricular Ito,f channels.</description><subject>Animals</subject><subject>Cardiovascular</subject><subject>Electrophysiology</subject><subject>Gene Expression Regulation</subject><subject>Gene Targeting</subject><subject>Heart Ventricles - metabolism</subject><subject>Ion Channel Gating</subject><subject>Life Sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Phenotype</subject><subject>Protein Subunits - genetics</subject><subject>Protein Subunits - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Shal Potassium Channels - chemistry</subject><subject>Shal Potassium Channels - genetics</subject><subject>Shal Potassium Channels - metabolism</subject><issn>0022-2828</issn><issn>1095-8584</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdUk1v1DAQtRCILoVfgIR8QqrUBH8lTi5IVUVpxUoc6N3yOuOuQ2K3dhJp_z0Ou6LAaazxvDfz5g1C7ykpKaH1p7489KMxJSNE5kyZwwu0oaStiqZqxEu0IYSxgjWsOUNvUuoJIa3g_DU6ow0RVU35Bqlviyg5dgn7MOEIT7OL0GEbIp72gB_AQ9STCx4Hi-3szfrWA76bwqXFZq-9hyFh57Hu5mHCY5gT4AX8FJ0ZIL1Fr6weErw7xXN0f_Pl_vq22H7_end9tS2MIFIWxlaWCk6hNnXbmaoC1sld1dQMeMt3zHaMcagZly1tW9FJJkgnWM2axoJk_Bx9PtI-zrsROrP214N6jG7U8aCCdurfH-_26iEsijFR5W1lgosjwf4_2O3VVq05wnidu5OF5tqPp2YxPM2QJjW6ZGAYtIcsX8nsTlNLmQv5sdDEkFIE-4eZErV6qHr120O1ergmc8ioD39recacTHsWmzcPi4OozOC8M3r4CQdIfZhjtigpqhJTRP1Yz2C9ApIHY5IL_gtMN63d</recordid><startdate>200801</startdate><enddate>200801</enddate><creator>Niwa, Noriko</creator><creator>Wang, Wei</creator><creator>Sha, Qun</creator><creator>Marionneau, Céline</creator><creator>Nerbonne, Jeanne M</creator><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>1XC</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-0962-9756</orcidid></search><sort><creationdate>200801</creationdate><title>Kv4.3 is not required for the generation of functional Ito,f channels in adult mouse ventricles</title><author>Niwa, Noriko ; Wang, Wei ; Sha, Qun ; Marionneau, Céline ; Nerbonne, Jeanne M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4077-cf5f1431e6c69dc55e2d7b5862e393b2fd223e623791994d7240d426288fe723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Cardiovascular</topic><topic>Electrophysiology</topic><topic>Gene Expression Regulation</topic><topic>Gene Targeting</topic><topic>Heart Ventricles - metabolism</topic><topic>Ion Channel Gating</topic><topic>Life Sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Phenotype</topic><topic>Protein Subunits - genetics</topic><topic>Protein Subunits - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Shal Potassium Channels - chemistry</topic><topic>Shal Potassium Channels - genetics</topic><topic>Shal Potassium Channels - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Niwa, Noriko</creatorcontrib><creatorcontrib>Wang, Wei</creatorcontrib><creatorcontrib>Sha, Qun</creatorcontrib><creatorcontrib>Marionneau, Céline</creatorcontrib><creatorcontrib>Nerbonne, Jeanne M</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>Hyper Article en Ligne (HAL)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>J Mol Cell Cardiol</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Niwa, Noriko</au><au>Wang, Wei</au><au>Sha, Qun</au><au>Marionneau, Céline</au><au>Nerbonne, Jeanne M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kv4.3 is not required for the generation of functional Ito,f channels in adult mouse ventricles</atitle><jtitle>J Mol Cell Cardiol</jtitle><addtitle>J Mol Cell Cardiol</addtitle><date>2008-01</date><risdate>2008</risdate><volume>44</volume><issue>1</issue><spage>95</spage><epage>104</epage><pages>95-104</pages><issn>0022-2828</issn><eissn>1095-8584</eissn><abstract>Abstract Accumulated evidence suggests that the heteromeric assembly of Kv4.2 and Kv4.3 α-subunits underlies the fast transient Kv current ( Ito,f ) in rodent ventricles. Recent studies, however, demonstrated that the targeted deletion of Kv4.2 results in the complete elimination of Ito,f in adult mouse ventricles, revealing an essential role for the Kv4.2 α-subunit in the generation of mouse ventricular Ito,f channels. The present study was undertaken to investigate directly the functional role of Kv4.3 by examining the effects of the targeted disruption of the KCND3 (Kv4.3) locus. Mice lacking Kv4.3 (Kv4.3−/−) appear indistinguishable from wild-type control animals, and no structural or functional abnormalities were evident in Kv4.3−/− hearts. Voltage-clamp recordings revealed that functional Ito,f channels are expressed in Kv4.3−/− ventricular myocytes, and that mean Ito,f densities are similar to those recorded from wild-type cells. In addition, Ito,f properties (inactivation rates, voltage dependences of inactivation and rates of recovery from inactivation) in Kv4.3−/− and wild-type mouse ventricular myocytes were indistinguishable. Quantitative RT-PCR and Western blot analyses did not reveal any measurable changes in the expression of Kv4.2 or the Kv channel interacting protein (KChIP2) in Kv4.3−/− ventricles. Taken together, the results presented here suggest that, in contrast with Kv4.2, Kv4.3 is not required for the generation of functional mouse ventricular Ito,f channels.</abstract><cop>England</cop><pmid>18045613</pmid><doi>10.1016/j.yjmcc.2007.10.007</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-0962-9756</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animals Cardiovascular Electrophysiology Gene Expression Regulation Gene Targeting Heart Ventricles - metabolism Ion Channel Gating Life Sciences Mice Mice, Inbred C57BL Myocytes, Cardiac - metabolism Phenotype Protein Subunits - genetics Protein Subunits - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Shal Potassium Channels - chemistry Shal Potassium Channels - genetics Shal Potassium Channels - metabolism |
title | Kv4.3 is not required for the generation of functional Ito,f channels in adult mouse ventricles |
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