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Dynamic regulation of sodium/calcium exchange function in human heart failure
Sarcolemmal Na/Ca exchange (NCX) regulates cardiac Ca and contractility. NCX function during the cardiac cycle is determined by intracellular [Ca] and [Na] ([Ca]i, and [Na]i) and membrane potential (Em), which all change in human heart failure (HF). Therefore, changes in NCX function may contribute...
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Published in: | Circulation (New York, N.Y.) N.Y.), 2003-11, Vol.108 (18), p.2224-2229 |
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creator | WEBER, Christopher R PIACENTINO, Valentino III HOUSER, Steven R BERS, Donald M |
description | Sarcolemmal Na/Ca exchange (NCX) regulates cardiac Ca and contractility. NCX function during the cardiac cycle is determined by intracellular [Ca] and [Na] ([Ca]i, and [Na]i) and membrane potential (Em), which all change in human heart failure (HF). Therefore, changes in NCX function may contribute to abnormal Ca regulation in human HF.
We assessed the cellular bases of differences in NCX function in ventricular myocytes from failing (F) and nonfailing (NF) human hearts. Allosteric activation of NCX by [Ca]i was comparable in F and NF myocytes (K1/2=150+/-31 nmol/L, n=7). The steady-state relation between [Ca]i and NCX current (INCX) was used to infer the local submembrane [Ca]i ([Ca]sm) that is sensed by NCX dynamically during the action potential (AP) and Ca transient (37 degrees C). This involved "tail" INCX measurement during abrupt repolarization of APs and Ca transients, where peak inward INCX indicates [Ca]sm. This allows inference of the direction of Ca transport by the NCX during the AP. In NF myocytes, NCX extrudes Ca for most of the AP. Three factors shift the direction of NCX-mediated Ca transport (to favor more Ca influx) in F versus NF myocytes, as follows: (1) reduced [Ca]sm, (2) prolonged AP duration, and (3) elevated [Na]i.
These results show that Ca entry through NCX may limit systolic dysfunction due to reduced sarcoplasmic reticulum Ca stores in HF but could contribute to slow decay of the [Ca]i transient and to diastolic dysfunction. |
doi_str_mv | 10.1161/01.cir.0000095274.72486.94 |
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We assessed the cellular bases of differences in NCX function in ventricular myocytes from failing (F) and nonfailing (NF) human hearts. Allosteric activation of NCX by [Ca]i was comparable in F and NF myocytes (K1/2=150+/-31 nmol/L, n=7). The steady-state relation between [Ca]i and NCX current (INCX) was used to infer the local submembrane [Ca]i ([Ca]sm) that is sensed by NCX dynamically during the action potential (AP) and Ca transient (37 degrees C). This involved "tail" INCX measurement during abrupt repolarization of APs and Ca transients, where peak inward INCX indicates [Ca]sm. This allows inference of the direction of Ca transport by the NCX during the AP. In NF myocytes, NCX extrudes Ca for most of the AP. Three factors shift the direction of NCX-mediated Ca transport (to favor more Ca influx) in F versus NF myocytes, as follows: (1) reduced [Ca]sm, (2) prolonged AP duration, and (3) elevated [Na]i.
These results show that Ca entry through NCX may limit systolic dysfunction due to reduced sarcoplasmic reticulum Ca stores in HF but could contribute to slow decay of the [Ca]i transient and to diastolic dysfunction.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.cir.0000095274.72486.94</identifier><identifier>PMID: 14557358</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Action Potentials - drug effects ; Allosteric Regulation - drug effects ; Biological and medical sciences ; Blood and lymphatic vessels ; Calcium - metabolism ; Calcium - pharmacology ; Cardiology. Vascular system ; Cell Separation ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Electrophysiology ; Heart Failure - metabolism ; Humans ; Ion Transport - drug effects ; Medical sciences ; Myocardial Contraction ; Myocytes, Cardiac - metabolism ; Sodium - metabolism ; Sodium - pharmacology ; Sodium-Calcium Exchanger - drug effects ; Sodium-Calcium Exchanger - metabolism ; Space life sciences</subject><ispartof>Circulation (New York, N.Y.), 2003-11, Vol.108 (18), p.2224-2229</ispartof><rights>2004 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Nov 4 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c533t-d590053159339de00fe65a15c0295d8cf63016784abc729e337a372875c5d18f3</citedby><cites>FETCH-LOGICAL-c533t-d590053159339de00fe65a15c0295d8cf63016784abc729e337a372875c5d18f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15288655$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14557358$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>WEBER, Christopher R</creatorcontrib><creatorcontrib>PIACENTINO, Valentino III</creatorcontrib><creatorcontrib>HOUSER, Steven R</creatorcontrib><creatorcontrib>BERS, Donald M</creatorcontrib><title>Dynamic regulation of sodium/calcium exchange function in human heart failure</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Sarcolemmal Na/Ca exchange (NCX) regulates cardiac Ca and contractility. NCX function during the cardiac cycle is determined by intracellular [Ca] and [Na] ([Ca]i, and [Na]i) and membrane potential (Em), which all change in human heart failure (HF). Therefore, changes in NCX function may contribute to abnormal Ca regulation in human HF.
We assessed the cellular bases of differences in NCX function in ventricular myocytes from failing (F) and nonfailing (NF) human hearts. Allosteric activation of NCX by [Ca]i was comparable in F and NF myocytes (K1/2=150+/-31 nmol/L, n=7). The steady-state relation between [Ca]i and NCX current (INCX) was used to infer the local submembrane [Ca]i ([Ca]sm) that is sensed by NCX dynamically during the action potential (AP) and Ca transient (37 degrees C). This involved "tail" INCX measurement during abrupt repolarization of APs and Ca transients, where peak inward INCX indicates [Ca]sm. This allows inference of the direction of Ca transport by the NCX during the AP. In NF myocytes, NCX extrudes Ca for most of the AP. Three factors shift the direction of NCX-mediated Ca transport (to favor more Ca influx) in F versus NF myocytes, as follows: (1) reduced [Ca]sm, (2) prolonged AP duration, and (3) elevated [Na]i.
These results show that Ca entry through NCX may limit systolic dysfunction due to reduced sarcoplasmic reticulum Ca stores in HF but could contribute to slow decay of the [Ca]i transient and to diastolic dysfunction.</description><subject>Action Potentials - drug effects</subject><subject>Allosteric Regulation - drug effects</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Calcium - metabolism</subject><subject>Calcium - pharmacology</subject><subject>Cardiology. Vascular system</subject><subject>Cell Separation</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Electrophysiology</subject><subject>Heart Failure - metabolism</subject><subject>Humans</subject><subject>Ion Transport - drug effects</subject><subject>Medical sciences</subject><subject>Myocardial Contraction</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Sodium - metabolism</subject><subject>Sodium - pharmacology</subject><subject>Sodium-Calcium Exchanger - drug effects</subject><subject>Sodium-Calcium Exchanger - metabolism</subject><subject>Space life sciences</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNpdkF1rHCEUhqW0NJs0f6EMC-3dTNTjGbV3ZZukgYRAaK7FOJp1mY-trtD8-8wmCwv1wsPB5z1HHkKWjDaMteyCssbF1ND90cilaCQXqm20-EAWDLmoBYL-SBb791oC5yfkNOfN3LYg8TM5YQJRAqoFufv1Mtohuir559LbXZzGagpVnrpYhgtnezfXyv9zazs--yqU0b0xcazWZbDz7W3aVcHGviT_hXwKts_-_FDPyOPV5Z_V7_r2_vpm9fO2dgiwqzvUlCIw1AC685QG36Jl6CjX2CkXWqCslUrYJye59gDSguRKosOOqQBn5Pv73G2a_hafd2aI2fm-t6OfSjaSAQih9Qwu_wM3U0nj_DfDGZfIUO2hH--QS1POyQezTXGw6cUwavbGDWVmdfNgjsbNm3GjxRz-ethQngbfHaMHxTPw7QDYPPsMyY4u5iOHXKkWEV4BZqSIag</recordid><startdate>20031104</startdate><enddate>20031104</enddate><creator>WEBER, Christopher R</creator><creator>PIACENTINO, Valentino III</creator><creator>HOUSER, Steven R</creator><creator>BERS, Donald M</creator><general>Lippincott Williams & Wilkins</general><general>American Heart Association, Inc</general><scope>IQODW</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>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope></search><sort><creationdate>20031104</creationdate><title>Dynamic regulation of sodium/calcium exchange function in human heart failure</title><author>WEBER, Christopher R ; PIACENTINO, Valentino III ; HOUSER, Steven R ; BERS, Donald M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c533t-d590053159339de00fe65a15c0295d8cf63016784abc729e337a372875c5d18f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Action Potentials - drug effects</topic><topic>Allosteric Regulation - drug effects</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Calcium - metabolism</topic><topic>Calcium - pharmacology</topic><topic>Cardiology. Vascular system</topic><topic>Cell Separation</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Electrophysiology</topic><topic>Heart Failure - metabolism</topic><topic>Humans</topic><topic>Ion Transport - drug effects</topic><topic>Medical sciences</topic><topic>Myocardial Contraction</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Sodium - metabolism</topic><topic>Sodium - pharmacology</topic><topic>Sodium-Calcium Exchanger - drug effects</topic><topic>Sodium-Calcium Exchanger - metabolism</topic><topic>Space life sciences</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>WEBER, Christopher R</creatorcontrib><creatorcontrib>PIACENTINO, Valentino III</creatorcontrib><creatorcontrib>HOUSER, Steven R</creatorcontrib><creatorcontrib>BERS, Donald M</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>WEBER, Christopher R</au><au>PIACENTINO, Valentino III</au><au>HOUSER, Steven R</au><au>BERS, Donald M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dynamic regulation of sodium/calcium exchange function in human heart failure</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2003-11-04</date><risdate>2003</risdate><volume>108</volume><issue>18</issue><spage>2224</spage><epage>2229</epage><pages>2224-2229</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Sarcolemmal Na/Ca exchange (NCX) regulates cardiac Ca and contractility. NCX function during the cardiac cycle is determined by intracellular [Ca] and [Na] ([Ca]i, and [Na]i) and membrane potential (Em), which all change in human heart failure (HF). Therefore, changes in NCX function may contribute to abnormal Ca regulation in human HF.
We assessed the cellular bases of differences in NCX function in ventricular myocytes from failing (F) and nonfailing (NF) human hearts. Allosteric activation of NCX by [Ca]i was comparable in F and NF myocytes (K1/2=150+/-31 nmol/L, n=7). The steady-state relation between [Ca]i and NCX current (INCX) was used to infer the local submembrane [Ca]i ([Ca]sm) that is sensed by NCX dynamically during the action potential (AP) and Ca transient (37 degrees C). This involved "tail" INCX measurement during abrupt repolarization of APs and Ca transients, where peak inward INCX indicates [Ca]sm. This allows inference of the direction of Ca transport by the NCX during the AP. In NF myocytes, NCX extrudes Ca for most of the AP. Three factors shift the direction of NCX-mediated Ca transport (to favor more Ca influx) in F versus NF myocytes, as follows: (1) reduced [Ca]sm, (2) prolonged AP duration, and (3) elevated [Na]i.
These results show that Ca entry through NCX may limit systolic dysfunction due to reduced sarcoplasmic reticulum Ca stores in HF but could contribute to slow decay of the [Ca]i transient and to diastolic dysfunction.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>14557358</pmid><doi>10.1161/01.cir.0000095274.72486.94</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Action Potentials - drug effects Allosteric Regulation - drug effects Biological and medical sciences Blood and lymphatic vessels Calcium - metabolism Calcium - pharmacology Cardiology. Vascular system Cell Separation Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Electrophysiology Heart Failure - metabolism Humans Ion Transport - drug effects Medical sciences Myocardial Contraction Myocytes, Cardiac - metabolism Sodium - metabolism Sodium - pharmacology Sodium-Calcium Exchanger - drug effects Sodium-Calcium Exchanger - metabolism Space life sciences |
title | Dynamic regulation of sodium/calcium exchange function in human heart failure |
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