Identification of a specific role for the Na,K-ATPase alpha 2 isoform as a regulator of calcium in the heart
It is well accepted that inhibition of the Na,K-ATPase in the heart, through effects on the Na/Ca exchanger, raises the intracellular Ca2+ concentration and strengthens cardiac contraction. However, the contribution that individual isoforms make to this calcium regulatory role is unknown. Assessing...
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| Veröffentlicht in: | Molecular cell 1999-05, Vol.3 (5), p.555-563 |
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| creator | James, P F Grupp, I L Grupp, G Woo, A L Askew, G R Croyle, M L Walsh, R A Lingrel, J B |
| description | It is well accepted that inhibition of the Na,K-ATPase in the heart, through effects on the Na/Ca exchanger, raises the intracellular Ca2+ concentration and strengthens cardiac contraction. However, the contribution that individual isoforms make to this calcium regulatory role is unknown. Assessing the phenotypes of mouse hearts with genetically reduced levels of Na,K-ATPase alpha 1 or alpha 2 isoforms clearly demonstrates different functional roles for these isoforms in vivo. Heterozygous alpha 2 hearts are hypercontractile as a result of increased calcium transients during the contractile cycle. In contrast, heterozygous alpha 1 hearts are hypocontractile. The different functional roles of these two isoforms are further demonstrated since inhibition of the alpha 2 isoform with ouabain increases the contractility of heterozygous alpha 1 hearts. These results definitively illustrate a specific role for the alpha 2 Na,K-ATPase isoform in Ca2+ signaling during cardiac contraction. |
| doi_str_mv | 10.1016/S1097-2765(00)80349-4 |
| format | Article |
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However, the contribution that individual isoforms make to this calcium regulatory role is unknown. Assessing the phenotypes of mouse hearts with genetically reduced levels of Na,K-ATPase alpha 1 or alpha 2 isoforms clearly demonstrates different functional roles for these isoforms in vivo. Heterozygous alpha 2 hearts are hypercontractile as a result of increased calcium transients during the contractile cycle. In contrast, heterozygous alpha 1 hearts are hypocontractile. The different functional roles of these two isoforms are further demonstrated since inhibition of the alpha 2 isoform with ouabain increases the contractility of heterozygous alpha 1 hearts. These results definitively illustrate a specific role for the alpha 2 Na,K-ATPase isoform in Ca2+ signaling during cardiac contraction.</description><identifier>ISSN: 1097-2765</identifier><identifier>ISSN: 1097-4164</identifier><identifier>DOI: 10.1016/S1097-2765(00)80349-4</identifier><identifier>PMID: 10360172</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Calcium - metabolism ; Calcium Signaling - physiology ; Enzyme Inhibitors - pharmacology ; Glycosides - pharmacology ; Heart Failure - enzymology ; Heart Ventricles - cytology ; Heart Ventricles - enzymology ; Heterozygote ; Isoenzymes - antagonists & inhibitors ; Isoenzymes - genetics ; Isoenzymes - metabolism ; Mice ; Mice, Transgenic ; Muscle Fibers, Skeletal - enzymology ; Myocardial Contraction - drug effects ; Myocardial Contraction - physiology ; Myocardium - cytology ; Myocardium - enzymology ; Ouabain - pharmacology ; RNA, Messenger - metabolism ; Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors ; Sodium-Potassium-Exchanging ATPase - genetics ; Sodium-Potassium-Exchanging ATPase - metabolism ; Stem Cells</subject><ispartof>Molecular cell, 1999-05, Vol.3 (5), p.555-563</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10360172$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>James, P F</creatorcontrib><creatorcontrib>Grupp, I L</creatorcontrib><creatorcontrib>Grupp, G</creatorcontrib><creatorcontrib>Woo, A L</creatorcontrib><creatorcontrib>Askew, G R</creatorcontrib><creatorcontrib>Croyle, M L</creatorcontrib><creatorcontrib>Walsh, R A</creatorcontrib><creatorcontrib>Lingrel, J B</creatorcontrib><title>Identification of a specific role for the Na,K-ATPase alpha 2 isoform as a regulator of calcium in the heart</title><title>Molecular cell</title><addtitle>Mol Cell</addtitle><description>It is well accepted that inhibition of the Na,K-ATPase in the heart, through effects on the Na/Ca exchanger, raises the intracellular Ca2+ concentration and strengthens cardiac contraction. However, the contribution that individual isoforms make to this calcium regulatory role is unknown. Assessing the phenotypes of mouse hearts with genetically reduced levels of Na,K-ATPase alpha 1 or alpha 2 isoforms clearly demonstrates different functional roles for these isoforms in vivo. Heterozygous alpha 2 hearts are hypercontractile as a result of increased calcium transients during the contractile cycle. In contrast, heterozygous alpha 1 hearts are hypocontractile. The different functional roles of these two isoforms are further demonstrated since inhibition of the alpha 2 isoform with ouabain increases the contractility of heterozygous alpha 1 hearts. These results definitively illustrate a specific role for the alpha 2 Na,K-ATPase isoform in Ca2+ signaling during cardiac contraction.</description><subject>Animals</subject><subject>Calcium - metabolism</subject><subject>Calcium Signaling - physiology</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Glycosides - pharmacology</subject><subject>Heart Failure - enzymology</subject><subject>Heart Ventricles - cytology</subject><subject>Heart Ventricles - enzymology</subject><subject>Heterozygote</subject><subject>Isoenzymes - antagonists & inhibitors</subject><subject>Isoenzymes - genetics</subject><subject>Isoenzymes - metabolism</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Muscle Fibers, Skeletal - enzymology</subject><subject>Myocardial Contraction - drug effects</subject><subject>Myocardial Contraction - physiology</subject><subject>Myocardium - cytology</subject><subject>Myocardium - enzymology</subject><subject>Ouabain - pharmacology</subject><subject>RNA, Messenger - metabolism</subject><subject>Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors</subject><subject>Sodium-Potassium-Exchanging ATPase - genetics</subject><subject>Sodium-Potassium-Exchanging ATPase - metabolism</subject><subject>Stem Cells</subject><issn>1097-2765</issn><issn>1097-4164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtOwzAURL0A0VL4BJBXCCQCvnYcJ0tU8aioAImyjm7Sa2rkPIiTBX9PgMKW1UgzZ2YxjB2BuAAByeUziMxE0iT6VIizVKg4i-IdNv2zJ2w_hDchINZptscmIFQiwMgp84s11b2zrsTeNTVvLEceWiq_LN41nrhtOt5viD_g-X10tXrCQBx9u0EuuQvNGFccw1jr6HXw2I_4uFKiL91QcVd_lzeEXX_Adi36QIdbnbGXm-vV_C5aPt4u5lfLqAUj-khnQtgULFkoYiqFjgsqk9hiatFKJQm1VilkRpEy2kqAtJBodIJKK61JzdjJz27bNe8DhT6vXCjJe6ypGUKeZOn4jJL_gmCUzqSEETzegkNR0TpvO1dh95H_Hqk-ASa4ctA</recordid><startdate>199905</startdate><enddate>199905</enddate><creator>James, P F</creator><creator>Grupp, I L</creator><creator>Grupp, G</creator><creator>Woo, A L</creator><creator>Askew, G R</creator><creator>Croyle, M L</creator><creator>Walsh, R A</creator><creator>Lingrel, J B</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QP</scope><scope>7X8</scope></search><sort><creationdate>199905</creationdate><title>Identification of a specific role for the Na,K-ATPase alpha 2 isoform as a regulator of calcium in the heart</title><author>James, P F ; Grupp, I L ; Grupp, G ; Woo, A L ; Askew, G R ; Croyle, M L ; Walsh, R A ; Lingrel, J B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p170t-5900f81fef1b4ec054bec64fa8faf232ea55381973e375f2118b2a756a35355e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Animals</topic><topic>Calcium - metabolism</topic><topic>Calcium Signaling - physiology</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Glycosides - pharmacology</topic><topic>Heart Failure - enzymology</topic><topic>Heart Ventricles - cytology</topic><topic>Heart Ventricles - enzymology</topic><topic>Heterozygote</topic><topic>Isoenzymes - antagonists & inhibitors</topic><topic>Isoenzymes - genetics</topic><topic>Isoenzymes - metabolism</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Muscle Fibers, Skeletal - enzymology</topic><topic>Myocardial Contraction - drug effects</topic><topic>Myocardial Contraction - physiology</topic><topic>Myocardium - cytology</topic><topic>Myocardium - enzymology</topic><topic>Ouabain - pharmacology</topic><topic>RNA, Messenger - metabolism</topic><topic>Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors</topic><topic>Sodium-Potassium-Exchanging ATPase - genetics</topic><topic>Sodium-Potassium-Exchanging ATPase - metabolism</topic><topic>Stem Cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>James, P F</creatorcontrib><creatorcontrib>Grupp, I L</creatorcontrib><creatorcontrib>Grupp, G</creatorcontrib><creatorcontrib>Woo, A L</creatorcontrib><creatorcontrib>Askew, G R</creatorcontrib><creatorcontrib>Croyle, M L</creatorcontrib><creatorcontrib>Walsh, R A</creatorcontrib><creatorcontrib>Lingrel, J B</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>James, P F</au><au>Grupp, I L</au><au>Grupp, G</au><au>Woo, A L</au><au>Askew, G R</au><au>Croyle, M L</au><au>Walsh, R A</au><au>Lingrel, J B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of a specific role for the Na,K-ATPase alpha 2 isoform as a regulator of calcium in the heart</atitle><jtitle>Molecular cell</jtitle><addtitle>Mol Cell</addtitle><date>1999-05</date><risdate>1999</risdate><volume>3</volume><issue>5</issue><spage>555</spage><epage>563</epage><pages>555-563</pages><issn>1097-2765</issn><issn>1097-4164</issn><abstract>It is well accepted that inhibition of the Na,K-ATPase in the heart, through effects on the Na/Ca exchanger, raises the intracellular Ca2+ concentration and strengthens cardiac contraction. However, the contribution that individual isoforms make to this calcium regulatory role is unknown. Assessing the phenotypes of mouse hearts with genetically reduced levels of Na,K-ATPase alpha 1 or alpha 2 isoforms clearly demonstrates different functional roles for these isoforms in vivo. Heterozygous alpha 2 hearts are hypercontractile as a result of increased calcium transients during the contractile cycle. In contrast, heterozygous alpha 1 hearts are hypocontractile. The different functional roles of these two isoforms are further demonstrated since inhibition of the alpha 2 isoform with ouabain increases the contractility of heterozygous alpha 1 hearts. These results definitively illustrate a specific role for the alpha 2 Na,K-ATPase isoform in Ca2+ signaling during cardiac contraction.</abstract><cop>United States</cop><pmid>10360172</pmid><doi>10.1016/S1097-2765(00)80349-4</doi><tpages>9</tpages></addata></record> |
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| source | MEDLINE; Cell Press Archives; Elsevier ScienceDirect Journals Complete; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | Animals Calcium - metabolism Calcium Signaling - physiology Enzyme Inhibitors - pharmacology Glycosides - pharmacology Heart Failure - enzymology Heart Ventricles - cytology Heart Ventricles - enzymology Heterozygote Isoenzymes - antagonists & inhibitors Isoenzymes - genetics Isoenzymes - metabolism Mice Mice, Transgenic Muscle Fibers, Skeletal - enzymology Myocardial Contraction - drug effects Myocardial Contraction - physiology Myocardium - cytology Myocardium - enzymology Ouabain - pharmacology RNA, Messenger - metabolism Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors Sodium-Potassium-Exchanging ATPase - genetics Sodium-Potassium-Exchanging ATPase - metabolism Stem Cells |
| title | Identification of a specific role for the Na,K-ATPase alpha 2 isoform as a regulator of calcium in the heart |
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