Cellular Basis of Abnormal Calcium Transients of Failing Human Ventricular Myocytes
ABSTRACT—Depressed contractility is a central feature of the failing human heart and has been attributed to altered [Ca]i. This study examined the respective roles of the L-type Ca current (ICa), SR Ca uptake, storage and release, Ca transport via the Na-Ca exchanger (NCX), and Ca buffering in the a...
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| Veröffentlicht in: | Circulation research 2003-04, Vol.92 (6), p.651-658 |
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| creator | Piacentino, Valentino Weber, Christopher R Chen, Xiongwen Weisser-Thomas, Jutta Margulies, Kenneth B Bers, Donald M Houser, Steven R |
| description | ABSTRACT—Depressed contractility is a central feature of the failing human heart and has been attributed to altered [Ca]i. This study examined the respective roles of the L-type Ca current (ICa), SR Ca uptake, storage and release, Ca transport via the Na-Ca exchanger (NCX), and Ca buffering in the altered Ca transients of failing human ventricular myocytes. Electrophysiological techniques were used to measure and control Vm and measure Im, respectively, and Fluo-3 was used to measure [Ca]i in myocytes from nonfailing (NF) and failing (F) human hearts. Ca transients from F myocytes were significantly smaller and decayed more slowly than those from NF hearts. Ca uptake rates by the SR and the amount of Ca stored in the SR were significantly reduced in F myocytes. There were no significant changes in the rate of Ca removal from F myocytes by the NCX, in the density of NCX current as a function of [Ca]i, ICa density, or cellular Ca buffering. However, Ca influx during the late portions of the action potential seems able to elevate [Ca]i in F but not in NF myocytes. A reduction in the rate of net Ca uptake by the SR slows the decay of the Ca transient and reduces SR Ca stores. This leads to reduced SR Ca release, which induces additional Ca influx during the plateau phase of the action potential, further slowing the decay of the Ca transient. These changes can explain the defective Ca transients of the failing human ventricular myocyte. |
| doi_str_mv | 10.1161/01.RES.0000062469.83985.9B |
| format | Article |
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This study examined the respective roles of the L-type Ca current (ICa), SR Ca uptake, storage and release, Ca transport via the Na-Ca exchanger (NCX), and Ca buffering in the altered Ca transients of failing human ventricular myocytes. Electrophysiological techniques were used to measure and control Vm and measure Im, respectively, and Fluo-3 was used to measure [Ca]i in myocytes from nonfailing (NF) and failing (F) human hearts. Ca transients from F myocytes were significantly smaller and decayed more slowly than those from NF hearts. Ca uptake rates by the SR and the amount of Ca stored in the SR were significantly reduced in F myocytes. There were no significant changes in the rate of Ca removal from F myocytes by the NCX, in the density of NCX current as a function of [Ca]i, ICa density, or cellular Ca buffering. However, Ca influx during the late portions of the action potential seems able to elevate [Ca]i in F but not in NF myocytes. A reduction in the rate of net Ca uptake by the SR slows the decay of the Ca transient and reduces SR Ca stores. This leads to reduced SR Ca release, which induces additional Ca influx during the plateau phase of the action potential, further slowing the decay of the Ca transient. These changes can explain the defective Ca transients of the failing human ventricular myocyte.</description><identifier>ISSN: 0009-7330</identifier><identifier>EISSN: 1524-4571</identifier><identifier>DOI: 10.1161/01.RES.0000062469.83985.9B</identifier><identifier>PMID: 12600875</identifier><identifier>CODEN: CIRUAL</identifier><language>eng</language><publisher>Hagerstown, MD: American Heart Association, Inc</publisher><subject>Action Potentials ; Aged ; Biological and medical sciences ; Calcium - metabolism ; Calcium Signaling ; Calcium-Transporting ATPases - physiology ; Cardiology. Vascular system ; Electric Conductivity ; Female ; Heart ; Heart Failure - diagnosis ; Heart Failure - metabolism ; Heart Failure - physiopathology ; Heart failure, cardiogenic pulmonary edema, cardiac enlargement ; Heart Ventricles - cytology ; Humans ; Ion Transport ; Male ; Medical sciences ; Middle Aged ; Myocardial Contraction ; Myocytes, Cardiac - metabolism ; Myocytes, Cardiac - physiology ; Patch-Clamp Techniques ; Sarcoplasmic Reticulum - metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; Sodium-Calcium Exchanger - physiology ; Space life sciences</subject><ispartof>Circulation research, 2003-04, Vol.92 (6), p.651-658</ispartof><rights>2003 American Heart Association, Inc.</rights><rights>2003 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. 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This study examined the respective roles of the L-type Ca current (ICa), SR Ca uptake, storage and release, Ca transport via the Na-Ca exchanger (NCX), and Ca buffering in the altered Ca transients of failing human ventricular myocytes. Electrophysiological techniques were used to measure and control Vm and measure Im, respectively, and Fluo-3 was used to measure [Ca]i in myocytes from nonfailing (NF) and failing (F) human hearts. Ca transients from F myocytes were significantly smaller and decayed more slowly than those from NF hearts. Ca uptake rates by the SR and the amount of Ca stored in the SR were significantly reduced in F myocytes. There were no significant changes in the rate of Ca removal from F myocytes by the NCX, in the density of NCX current as a function of [Ca]i, ICa density, or cellular Ca buffering. However, Ca influx during the late portions of the action potential seems able to elevate [Ca]i in F but not in NF myocytes. A reduction in the rate of net Ca uptake by the SR slows the decay of the Ca transient and reduces SR Ca stores. This leads to reduced SR Ca release, which induces additional Ca influx during the plateau phase of the action potential, further slowing the decay of the Ca transient. These changes can explain the defective Ca transients of the failing human ventricular myocyte.</description><subject>Action Potentials</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Calcium - metabolism</subject><subject>Calcium Signaling</subject><subject>Calcium-Transporting ATPases - physiology</subject><subject>Cardiology. Vascular system</subject><subject>Electric Conductivity</subject><subject>Female</subject><subject>Heart</subject><subject>Heart Failure - diagnosis</subject><subject>Heart Failure - metabolism</subject><subject>Heart Failure - physiopathology</subject><subject>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</subject><subject>Heart Ventricles - cytology</subject><subject>Humans</subject><subject>Ion Transport</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Myocardial Contraction</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Myocytes, Cardiac - physiology</subject><subject>Patch-Clamp Techniques</subject><subject>Sarcoplasmic Reticulum - metabolism</subject><subject>Sarcoplasmic Reticulum Calcium-Transporting ATPases</subject><subject>Sodium-Calcium Exchanger - physiology</subject><subject>Space life sciences</subject><issn>0009-7330</issn><issn>1524-4571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkNtq3DAQhkVpabZpXqGYQHtnV6OTpd5ll6QppASSNLdC1kqNUtlOJZuwb1_tARYqXQzMfPPPzI_QOeAGQMBXDM3d5X2Dt08QJlQjqZK8Ucs3aAGcsJrxFt6iRamruqUUn6APOT9jDIwS9R6dABEYy5Yv0P3KxThHk6qlySFXo68uumFMvYnVykQb5r56SGbIwQ3TrnxlQgzD7-p67s1QPZZ0Cnan8HMz2s3k8kf0zpuY3dkhnqJfV5cPq-v65vb7j9XFTW0FkaKmnsu1LItQyYWUiuOWM0U76rHsJDeecUPajhjwnfPUrn1JWyCmMwpcIU_Rl73uSxr_zi5Pug_ZlnvM4MY565YCx6wVBTz_D3we5zSU3TQBwoiknBbo2x6yacw5Oa9fUuhN2mjAeuu7xqCL7_rou975rtWyNH86TJi73q2PrQejC_D5AJhsTfTFUhvykStqnLSkcGzPvY5xcin_ifOrS_rJmTg97UZTDKQm28jKr0sGBP0H8KeZ9w</recordid><startdate>20030404</startdate><enddate>20030404</enddate><creator>Piacentino, Valentino</creator><creator>Weber, Christopher R</creator><creator>Chen, Xiongwen</creator><creator>Weisser-Thomas, Jutta</creator><creator>Margulies, Kenneth B</creator><creator>Bers, Donald M</creator><creator>Houser, Steven R</creator><general>American Heart Association, Inc</general><general>Lippincott</general><general>Lippincott Williams & Wilkins Ovid Technologies</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>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20030404</creationdate><title>Cellular Basis of Abnormal Calcium Transients of Failing Human Ventricular Myocytes</title><author>Piacentino, Valentino ; Weber, Christopher R ; Chen, Xiongwen ; Weisser-Thomas, Jutta ; Margulies, Kenneth B ; Bers, Donald M ; Houser, Steven R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6286-3f58d860038568895075493b3f08b85af45a27b2a1fbef3cdf8b8c12aba91e493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Action Potentials</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Calcium - metabolism</topic><topic>Calcium Signaling</topic><topic>Calcium-Transporting ATPases - physiology</topic><topic>Cardiology. Vascular system</topic><topic>Electric Conductivity</topic><topic>Female</topic><topic>Heart</topic><topic>Heart Failure - diagnosis</topic><topic>Heart Failure - metabolism</topic><topic>Heart Failure - physiopathology</topic><topic>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</topic><topic>Heart Ventricles - cytology</topic><topic>Humans</topic><topic>Ion Transport</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Myocardial Contraction</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Myocytes, Cardiac - physiology</topic><topic>Patch-Clamp Techniques</topic><topic>Sarcoplasmic Reticulum - metabolism</topic><topic>Sarcoplasmic Reticulum Calcium-Transporting ATPases</topic><topic>Sodium-Calcium Exchanger - physiology</topic><topic>Space life sciences</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Piacentino, Valentino</creatorcontrib><creatorcontrib>Weber, Christopher R</creatorcontrib><creatorcontrib>Chen, Xiongwen</creatorcontrib><creatorcontrib>Weisser-Thomas, Jutta</creatorcontrib><creatorcontrib>Margulies, Kenneth B</creatorcontrib><creatorcontrib>Bers, Donald M</creatorcontrib><creatorcontrib>Houser, Steven R</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>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Piacentino, Valentino</au><au>Weber, Christopher R</au><au>Chen, Xiongwen</au><au>Weisser-Thomas, Jutta</au><au>Margulies, Kenneth B</au><au>Bers, Donald M</au><au>Houser, Steven R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cellular Basis of Abnormal Calcium Transients of Failing Human Ventricular Myocytes</atitle><jtitle>Circulation research</jtitle><addtitle>Circ Res</addtitle><date>2003-04-04</date><risdate>2003</risdate><volume>92</volume><issue>6</issue><spage>651</spage><epage>658</epage><pages>651-658</pages><issn>0009-7330</issn><eissn>1524-4571</eissn><coden>CIRUAL</coden><abstract>ABSTRACT—Depressed contractility is a central feature of the failing human heart and has been attributed to altered [Ca]i. This study examined the respective roles of the L-type Ca current (ICa), SR Ca uptake, storage and release, Ca transport via the Na-Ca exchanger (NCX), and Ca buffering in the altered Ca transients of failing human ventricular myocytes. Electrophysiological techniques were used to measure and control Vm and measure Im, respectively, and Fluo-3 was used to measure [Ca]i in myocytes from nonfailing (NF) and failing (F) human hearts. Ca transients from F myocytes were significantly smaller and decayed more slowly than those from NF hearts. Ca uptake rates by the SR and the amount of Ca stored in the SR were significantly reduced in F myocytes. There were no significant changes in the rate of Ca removal from F myocytes by the NCX, in the density of NCX current as a function of [Ca]i, ICa density, or cellular Ca buffering. However, Ca influx during the late portions of the action potential seems able to elevate [Ca]i in F but not in NF myocytes. A reduction in the rate of net Ca uptake by the SR slows the decay of the Ca transient and reduces SR Ca stores. This leads to reduced SR Ca release, which induces additional Ca influx during the plateau phase of the action potential, further slowing the decay of the Ca transient. These changes can explain the defective Ca transients of the failing human ventricular myocyte.</abstract><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>12600875</pmid><doi>10.1161/01.RES.0000062469.83985.9B</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete |
| subjects | Action Potentials Aged Biological and medical sciences Calcium - metabolism Calcium Signaling Calcium-Transporting ATPases - physiology Cardiology. Vascular system Electric Conductivity Female Heart Heart Failure - diagnosis Heart Failure - metabolism Heart Failure - physiopathology Heart failure, cardiogenic pulmonary edema, cardiac enlargement Heart Ventricles - cytology Humans Ion Transport Male Medical sciences Middle Aged Myocardial Contraction Myocytes, Cardiac - metabolism Myocytes, Cardiac - physiology Patch-Clamp Techniques Sarcoplasmic Reticulum - metabolism Sarcoplasmic Reticulum Calcium-Transporting ATPases Sodium-Calcium Exchanger - physiology Space life sciences |
| title | Cellular Basis of Abnormal Calcium Transients of Failing Human Ventricular Myocytes |
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