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Altered Cardiac Sarcoplasmic Reticulum Function of Intact Myocytes of Rat Ventricle During Metabolic Inhibition

ABSTRACT —Changes in the behavior of the sarcoplasmic reticulum (SR) in rat ventricular myocytes were investigated under conditions of metabolic inhibition using laser-scanning confocal microscopy to measure intracellular Ca and the perforated patch-clamp technique to measure SR Ca content. Metaboli...

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Published in:Circulation research 2001-02, Vol.88 (2), p.181-187
Main Authors: Overend, C L, Eisner, D A, O’Neill, S C
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Language:English
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description ABSTRACT —Changes in the behavior of the sarcoplasmic reticulum (SR) in rat ventricular myocytes were investigated under conditions of metabolic inhibition using laser-scanning confocal microscopy to measure intracellular Ca and the perforated patch-clamp technique to measure SR Ca content. Metabolic inhibition had several effects on SR function, including reduced frequency of spontaneous releases of Ca (sparks and waves of Ca-induced Ca release), increased SR Ca content (79.4±5.7 to 115.2±6.6 μmol/L cell volume [mean±SEM;P
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Metabolic inhibition had several effects on SR function, including reduced frequency of spontaneous releases of Ca (sparks and waves of Ca-induced Ca release), increased SR Ca content (79.4±5.7 to 115.2±6.6 μmol/L cell volume [mean±SEM;P &lt;0.001]), and, after a wave of Ca release, slower reuptake of Ca into the SR (rate constant of fall of Ca reduced from 8.5±1.1 s in control to 5.2±0.4 s in metabolic inhibition [P &lt;0.01]). Inhibition of L-type Ca channels with Cd (100 μmol/L) did not reproduce the effects of metabolic inhibition on spontaneous Ca sparks. These results are evidence of inhibition of both Ca release and reuptake mechanisms. Reduced frequency of release could be attributable to either of these effects, but the increased SR Ca content at the time of reduced frequency of spontaneous release of Ca shows that the dominant effect of metabolic inhibition is to inhibit release of Ca from the SR, allowing the accumulation of greater than normal amounts of Ca. In the context of ischemia, this extra accumulation of Ca would present a risk of potentially arrhythmogenic, spontaneous release of Ca on reperfusion of the tissue.</description><identifier>ISSN: 0009-7330</identifier><identifier>EISSN: 1524-4571</identifier><identifier>DOI: 10.1161/01.RES.88.2.181</identifier><identifier>PMID: 11157670</identifier><identifier>CODEN: CIRUAL</identifier><language>eng</language><publisher>Hagerstown, MD: American Heart Association, Inc</publisher><subject>Aniline Compounds ; Animals ; Biological and medical sciences ; Cadmium - pharmacology ; Calcium - metabolism ; Calcium Channel Blockers - pharmacology ; Calcium Channels, L-Type - metabolism ; Calcium Signaling - physiology ; Calcium-Transporting ATPases - antagonists &amp; inhibitors ; Calcium-Transporting ATPases - metabolism ; Cardiology. Vascular system ; Cells, Cultured ; Coronary heart disease ; Cyanides - pharmacology ; Deoxyglucose - pharmacology ; Fluorescent Dyes ; Heart ; Heart Ventricles - cytology ; Heart Ventricles - metabolism ; Intracellular Fluid - metabolism ; Medical sciences ; Microscopy, Confocal ; Myocardium - cytology ; Myocardium - metabolism ; Patch-Clamp Techniques ; Rats ; Ryanodine Receptor Calcium Release Channel - metabolism ; Sarcoplasmic Reticulum - metabolism ; Xanthenes</subject><ispartof>Circulation research, 2001-02, Vol.88 (2), p.181-187</ispartof><rights>2001 American Heart Association, Inc.</rights><rights>2001 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Feb 2, 2001</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4703-4450664bcb4089710535ed18f03f10baadb4dc8dc33a5c85effbfabd38122f8d3</citedby><cites>FETCH-LOGICAL-c4703-4450664bcb4089710535ed18f03f10baadb4dc8dc33a5c85effbfabd38122f8d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=897042$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11157670$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Overend, C L</creatorcontrib><creatorcontrib>Eisner, D A</creatorcontrib><creatorcontrib>O’Neill, S C</creatorcontrib><title>Altered Cardiac Sarcoplasmic Reticulum Function of Intact Myocytes of Rat Ventricle During Metabolic Inhibition</title><title>Circulation research</title><addtitle>Circ Res</addtitle><description>ABSTRACT —Changes in the behavior of the sarcoplasmic reticulum (SR) in rat ventricular myocytes were investigated under conditions of metabolic inhibition using laser-scanning confocal microscopy to measure intracellular Ca and the perforated patch-clamp technique to measure SR Ca content. Metabolic inhibition had several effects on SR function, including reduced frequency of spontaneous releases of Ca (sparks and waves of Ca-induced Ca release), increased SR Ca content (79.4±5.7 to 115.2±6.6 μmol/L cell volume [mean±SEM;P &lt;0.001]), and, after a wave of Ca release, slower reuptake of Ca into the SR (rate constant of fall of Ca reduced from 8.5±1.1 s in control to 5.2±0.4 s in metabolic inhibition [P &lt;0.01]). Inhibition of L-type Ca channels with Cd (100 μmol/L) did not reproduce the effects of metabolic inhibition on spontaneous Ca sparks. These results are evidence of inhibition of both Ca release and reuptake mechanisms. Reduced frequency of release could be attributable to either of these effects, but the increased SR Ca content at the time of reduced frequency of spontaneous release of Ca shows that the dominant effect of metabolic inhibition is to inhibit release of Ca from the SR, allowing the accumulation of greater than normal amounts of Ca. In the context of ischemia, this extra accumulation of Ca would present a risk of potentially arrhythmogenic, spontaneous release of Ca on reperfusion of the tissue.</description><subject>Aniline Compounds</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cadmium - pharmacology</subject><subject>Calcium - metabolism</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Calcium Channels, L-Type - metabolism</subject><subject>Calcium Signaling - physiology</subject><subject>Calcium-Transporting ATPases - antagonists &amp; inhibitors</subject><subject>Calcium-Transporting ATPases - metabolism</subject><subject>Cardiology. Vascular system</subject><subject>Cells, Cultured</subject><subject>Coronary heart disease</subject><subject>Cyanides - pharmacology</subject><subject>Deoxyglucose - pharmacology</subject><subject>Fluorescent Dyes</subject><subject>Heart</subject><subject>Heart Ventricles - cytology</subject><subject>Heart Ventricles - metabolism</subject><subject>Intracellular Fluid - metabolism</subject><subject>Medical sciences</subject><subject>Microscopy, Confocal</subject><subject>Myocardium - cytology</subject><subject>Myocardium - metabolism</subject><subject>Patch-Clamp Techniques</subject><subject>Rats</subject><subject>Ryanodine Receptor Calcium Release Channel - metabolism</subject><subject>Sarcoplasmic Reticulum - metabolism</subject><subject>Xanthenes</subject><issn>0009-7330</issn><issn>1524-4571</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><recordid>eNpdkdGL1DAQxoso3nr67JsUBd_am0nSNvt4rHe6cIewp76GNE3cnGmzJinH_vem7KIg8zAw_Objm_mK4i1CjdjiFWC9u3moOa9JjRyfFStsCKtY0-HzYgUA66qjFC6KVzE-AiCjZP2yuEDEpms7WBX-2iUd9FBuZBisVOWDDMofnIyjVeVOJ6tmN4_l7TypZP1UelNupyRVKu-PXh2TjstoJ1P5Q08pWOV0-WkOdvpZ3uske--yznba294u-6-LF0a6qN-c-2Xx_fbm2-ZLdff183ZzfVcp1gGtGGugbVmvegZ83SE0tNEDcgPUIPRSDj0bFB8UpbJRvNHG9Eb2A-VIiOEDvSw-nnQPwf-edUxitFFp5-Sk_RxFBy3jHV9n8P1_4KOfw5S9CYKEEZKfmKGrE6SCjzFoIw7BjjIcBYJYghCAIgchOBdE5CDyxruz7NyPevjHnz-fgQ9nQEYlnQlyUjb-5fLRwEim2Il68ktO8Zebn3QQey1d2gtYvAGSKptEILmqPEFK_wAFtKAg</recordid><startdate>20010202</startdate><enddate>20010202</enddate><creator>Overend, C L</creator><creator>Eisner, D A</creator><creator>O’Neill, S C</creator><general>American Heart Association, Inc</general><general>Lippincott</general><general>Lippincott Williams &amp; 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>20010202</creationdate><title>Altered Cardiac Sarcoplasmic Reticulum Function of Intact Myocytes of Rat Ventricle During Metabolic Inhibition</title><author>Overend, C L ; Eisner, D A ; O’Neill, S C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4703-4450664bcb4089710535ed18f03f10baadb4dc8dc33a5c85effbfabd38122f8d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Aniline Compounds</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cadmium - pharmacology</topic><topic>Calcium - metabolism</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Calcium Channels, L-Type - metabolism</topic><topic>Calcium Signaling - physiology</topic><topic>Calcium-Transporting ATPases - antagonists &amp; inhibitors</topic><topic>Calcium-Transporting ATPases - metabolism</topic><topic>Cardiology. Vascular system</topic><topic>Cells, Cultured</topic><topic>Coronary heart disease</topic><topic>Cyanides - pharmacology</topic><topic>Deoxyglucose - pharmacology</topic><topic>Fluorescent Dyes</topic><topic>Heart</topic><topic>Heart Ventricles - cytology</topic><topic>Heart Ventricles - metabolism</topic><topic>Intracellular Fluid - metabolism</topic><topic>Medical sciences</topic><topic>Microscopy, Confocal</topic><topic>Myocardium - cytology</topic><topic>Myocardium - metabolism</topic><topic>Patch-Clamp Techniques</topic><topic>Rats</topic><topic>Ryanodine Receptor Calcium Release Channel - metabolism</topic><topic>Sarcoplasmic Reticulum - metabolism</topic><topic>Xanthenes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Overend, C L</creatorcontrib><creatorcontrib>Eisner, D A</creatorcontrib><creatorcontrib>O’Neill, S C</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 &amp; Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; 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>Overend, C L</au><au>Eisner, D A</au><au>O’Neill, S C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered Cardiac Sarcoplasmic Reticulum Function of Intact Myocytes of Rat Ventricle During Metabolic Inhibition</atitle><jtitle>Circulation research</jtitle><addtitle>Circ Res</addtitle><date>2001-02-02</date><risdate>2001</risdate><volume>88</volume><issue>2</issue><spage>181</spage><epage>187</epage><pages>181-187</pages><issn>0009-7330</issn><eissn>1524-4571</eissn><coden>CIRUAL</coden><abstract>ABSTRACT —Changes in the behavior of the sarcoplasmic reticulum (SR) in rat ventricular myocytes were investigated under conditions of metabolic inhibition using laser-scanning confocal microscopy to measure intracellular Ca and the perforated patch-clamp technique to measure SR Ca content. Metabolic inhibition had several effects on SR function, including reduced frequency of spontaneous releases of Ca (sparks and waves of Ca-induced Ca release), increased SR Ca content (79.4±5.7 to 115.2±6.6 μmol/L cell volume [mean±SEM;P &lt;0.001]), and, after a wave of Ca release, slower reuptake of Ca into the SR (rate constant of fall of Ca reduced from 8.5±1.1 s in control to 5.2±0.4 s in metabolic inhibition [P &lt;0.01]). Inhibition of L-type Ca channels with Cd (100 μmol/L) did not reproduce the effects of metabolic inhibition on spontaneous Ca sparks. These results are evidence of inhibition of both Ca release and reuptake mechanisms. Reduced frequency of release could be attributable to either of these effects, but the increased SR Ca content at the time of reduced frequency of spontaneous release of Ca shows that the dominant effect of metabolic inhibition is to inhibit release of Ca from the SR, allowing the accumulation of greater than normal amounts of Ca. 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subjects Aniline Compounds
Animals
Biological and medical sciences
Cadmium - pharmacology
Calcium - metabolism
Calcium Channel Blockers - pharmacology
Calcium Channels, L-Type - metabolism
Calcium Signaling - physiology
Calcium-Transporting ATPases - antagonists & inhibitors
Calcium-Transporting ATPases - metabolism
Cardiology. Vascular system
Cells, Cultured
Coronary heart disease
Cyanides - pharmacology
Deoxyglucose - pharmacology
Fluorescent Dyes
Heart
Heart Ventricles - cytology
Heart Ventricles - metabolism
Intracellular Fluid - metabolism
Medical sciences
Microscopy, Confocal
Myocardium - cytology
Myocardium - metabolism
Patch-Clamp Techniques
Rats
Ryanodine Receptor Calcium Release Channel - metabolism
Sarcoplasmic Reticulum - metabolism
Xanthenes
title Altered Cardiac Sarcoplasmic Reticulum Function of Intact Myocytes of Rat Ventricle During Metabolic Inhibition
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