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Reduced synchrony of Ca2+ release with loss of T-tubules: a comparison to Ca2+ release in human failing cardiomyocytes
During cardiac excitation-contraction coupling, Ca2+ release from the sarcoplasmic reticulum (SR) occurs at the junctional complex with the T-tubules, containing the L-type Ca2+ channels. A partial loss of T-tubules has been described in myocytes from failing canine and human hearts. We examined how...
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Published in: | Cardiovascular research 2004-04, Vol.62 (1), p.63-73 |
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container_title | Cardiovascular research |
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creator | LOUCHA, William E BITO, Virginie HEINZEL, Frank R MACIANSKIENE, Regina VANHAECKEA, Johan FLAMENG, Willem MUBAGWA, Kanigula SIPIDO, Karin R |
description | During cardiac excitation-contraction coupling, Ca2+ release from the sarcoplasmic reticulum (SR) occurs at the junctional complex with the T-tubules, containing the L-type Ca2+ channels. A partial loss of T-tubules has been described in myocytes from failing canine and human hearts. We examined how graded reduction of T-tubule density would affect the synchrony of Ca2+ release.
Adult pig ventricular myocytes were isolated and cultured for 24 and 72 h. T-tubules, visualized with di-8-ANEPPS, and [Ca2+]i transients (Fluo-3) were recorded during confocal line scan imaging.
Cultured cardiomyocytes exhibited a progressive reduction in T-tubule density. [Ca2+]i transients showed small areas of delayed Ca2+ release which gradually increased in number and size with loss of T-tubules. Local [Ca2+]i transients in the delayed regions were reduced. Due to these changes, loss of T-tubules resulted in an overall slowing of the rise of [Ca2+] along the entire line scan and transient magnitude tended to be reduced, but there was no change in SR Ca2+ content. Human myocytes isolated from failing hearts had a T-tubule density comparable to that of freshly isolated pig myocytes. The size, but not the number, of delayed release areas tended to be larger. The overall rate of rise of [Ca2+]i was significantly faster than in pig myocytes with low T-tubule density.
Loss of T-tubules reduces the synchrony of SR Ca2+ release. This could contribute to reduced efficiency of excitation-contraction coupling in heart failure, though dyssynchrony in human failing cells appears to be modest. |
doi_str_mv | 10.1016/j.cardiores.2003.12.031 |
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Adult pig ventricular myocytes were isolated and cultured for 24 and 72 h. T-tubules, visualized with di-8-ANEPPS, and [Ca2+]i transients (Fluo-3) were recorded during confocal line scan imaging.
Cultured cardiomyocytes exhibited a progressive reduction in T-tubule density. [Ca2+]i transients showed small areas of delayed Ca2+ release which gradually increased in number and size with loss of T-tubules. Local [Ca2+]i transients in the delayed regions were reduced. Due to these changes, loss of T-tubules resulted in an overall slowing of the rise of [Ca2+] along the entire line scan and transient magnitude tended to be reduced, but there was no change in SR Ca2+ content. Human myocytes isolated from failing hearts had a T-tubule density comparable to that of freshly isolated pig myocytes. The size, but not the number, of delayed release areas tended to be larger. The overall rate of rise of [Ca2+]i was significantly faster than in pig myocytes with low T-tubule density.
Loss of T-tubules reduces the synchrony of SR Ca2+ release. This could contribute to reduced efficiency of excitation-contraction coupling in heart failure, though dyssynchrony in human failing cells appears to be modest.</description><identifier>ISSN: 0008-6363</identifier><identifier>EISSN: 1755-3245</identifier><identifier>DOI: 10.1016/j.cardiores.2003.12.031</identifier><identifier>PMID: 15023553</identifier><identifier>CODEN: CVREAU</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Animals ; Biological and medical sciences ; Calcium - metabolism ; Cardiology. Vascular system ; Cells, Cultured ; Electrophysiology ; Heart ; Heart Failure - metabolism ; Heart Failure - pathology ; Heart failure, cardiogenic pulmonary edema, cardiac enlargement ; Humans ; Image Processing, Computer-Assisted ; Medical sciences ; Microscopy, Confocal ; Myocytes, Cardiac - metabolism ; Myocytes, Cardiac - ultrastructure ; Sarcoplasmic Reticulum - ultrastructure ; Swine</subject><ispartof>Cardiovascular research, 2004-04, Vol.62 (1), p.63-73</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c320t-a89b1415d731be29bed02d3ab9c4a823f8d89d0125c5f2e82afae7178036e8c23</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15590920$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15023553$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>LOUCHA, William E</creatorcontrib><creatorcontrib>BITO, Virginie</creatorcontrib><creatorcontrib>HEINZEL, Frank R</creatorcontrib><creatorcontrib>MACIANSKIENE, Regina</creatorcontrib><creatorcontrib>VANHAECKEA, Johan</creatorcontrib><creatorcontrib>FLAMENG, Willem</creatorcontrib><creatorcontrib>MUBAGWA, Kanigula</creatorcontrib><creatorcontrib>SIPIDO, Karin R</creatorcontrib><title>Reduced synchrony of Ca2+ release with loss of T-tubules: a comparison to Ca2+ release in human failing cardiomyocytes</title><title>Cardiovascular research</title><addtitle>Cardiovasc Res</addtitle><description>During cardiac excitation-contraction coupling, Ca2+ release from the sarcoplasmic reticulum (SR) occurs at the junctional complex with the T-tubules, containing the L-type Ca2+ channels. A partial loss of T-tubules has been described in myocytes from failing canine and human hearts. We examined how graded reduction of T-tubule density would affect the synchrony of Ca2+ release.
Adult pig ventricular myocytes were isolated and cultured for 24 and 72 h. T-tubules, visualized with di-8-ANEPPS, and [Ca2+]i transients (Fluo-3) were recorded during confocal line scan imaging.
Cultured cardiomyocytes exhibited a progressive reduction in T-tubule density. [Ca2+]i transients showed small areas of delayed Ca2+ release which gradually increased in number and size with loss of T-tubules. Local [Ca2+]i transients in the delayed regions were reduced. Due to these changes, loss of T-tubules resulted in an overall slowing of the rise of [Ca2+] along the entire line scan and transient magnitude tended to be reduced, but there was no change in SR Ca2+ content. Human myocytes isolated from failing hearts had a T-tubule density comparable to that of freshly isolated pig myocytes. The size, but not the number, of delayed release areas tended to be larger. The overall rate of rise of [Ca2+]i was significantly faster than in pig myocytes with low T-tubule density.
Loss of T-tubules reduces the synchrony of SR Ca2+ release. This could contribute to reduced efficiency of excitation-contraction coupling in heart failure, though dyssynchrony in human failing cells appears to be modest.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Calcium - metabolism</subject><subject>Cardiology. Vascular system</subject><subject>Cells, Cultured</subject><subject>Electrophysiology</subject><subject>Heart</subject><subject>Heart Failure - metabolism</subject><subject>Heart Failure - pathology</subject><subject>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</subject><subject>Humans</subject><subject>Image Processing, Computer-Assisted</subject><subject>Medical sciences</subject><subject>Microscopy, Confocal</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Myocytes, Cardiac - ultrastructure</subject><subject>Sarcoplasmic Reticulum - ultrastructure</subject><subject>Swine</subject><issn>0008-6363</issn><issn>1755-3245</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><recordid>eNpVkFtr3DAQRkVJabZJ_0Krl_Sl2B1Jli95C0tvECiU5FmMpXFXi21tJLvB_75edunlSQw631wOY-8E5AJE-XGfW4zOh0gplwAqFzIHJV6wjai0zpQs9AXbAECdlapUl-x1Svu11LoqXrFLoUEqrdWG_fpBbrbkeFpGu4thXHjo-BblBx6pJ0zEn_20431I6fjzkE1zO_eUbjlyG4YDRp_CyKfwf8iPfDcPOPIOfe_Hn_y077AEu0yUrtnLDvtEb87vFXv8_Olh-zW7__7l2_buPrNKwpRh3bSiENpVSrQkm5YcSKewbWyBtVRd7erGgZDa6k5SLbFDqkRVgyqptlJdsfenvocYnmZKkxl8stT3OFKYk1lZBWVRrmB1Am1cL43UmUP0A8bFCDBH5WZv_ig3R-VGSLMqX5NvzyPmdiD3N3d2vAI3ZwCTxb6LOFqf_uF0A40E9RuNSo2l</recordid><startdate>20040401</startdate><enddate>20040401</enddate><creator>LOUCHA, William E</creator><creator>BITO, Virginie</creator><creator>HEINZEL, Frank R</creator><creator>MACIANSKIENE, Regina</creator><creator>VANHAECKEA, Johan</creator><creator>FLAMENG, Willem</creator><creator>MUBAGWA, Kanigula</creator><creator>SIPIDO, Karin R</creator><general>Oxford University Press</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>7X8</scope></search><sort><creationdate>20040401</creationdate><title>Reduced synchrony of Ca2+ release with loss of T-tubules: a comparison to Ca2+ release in human failing cardiomyocytes</title><author>LOUCHA, William E ; BITO, Virginie ; HEINZEL, Frank R ; MACIANSKIENE, Regina ; VANHAECKEA, Johan ; FLAMENG, Willem ; MUBAGWA, Kanigula ; SIPIDO, Karin R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c320t-a89b1415d731be29bed02d3ab9c4a823f8d89d0125c5f2e82afae7178036e8c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Calcium - metabolism</topic><topic>Cardiology. Vascular system</topic><topic>Cells, Cultured</topic><topic>Electrophysiology</topic><topic>Heart</topic><topic>Heart Failure - metabolism</topic><topic>Heart Failure - pathology</topic><topic>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</topic><topic>Humans</topic><topic>Image Processing, Computer-Assisted</topic><topic>Medical sciences</topic><topic>Microscopy, Confocal</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Myocytes, Cardiac - ultrastructure</topic><topic>Sarcoplasmic Reticulum - ultrastructure</topic><topic>Swine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>LOUCHA, William E</creatorcontrib><creatorcontrib>BITO, Virginie</creatorcontrib><creatorcontrib>HEINZEL, Frank R</creatorcontrib><creatorcontrib>MACIANSKIENE, Regina</creatorcontrib><creatorcontrib>VANHAECKEA, Johan</creatorcontrib><creatorcontrib>FLAMENG, Willem</creatorcontrib><creatorcontrib>MUBAGWA, Kanigula</creatorcontrib><creatorcontrib>SIPIDO, Karin 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>MEDLINE - Academic</collection><jtitle>Cardiovascular research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>LOUCHA, William E</au><au>BITO, Virginie</au><au>HEINZEL, Frank R</au><au>MACIANSKIENE, Regina</au><au>VANHAECKEA, Johan</au><au>FLAMENG, Willem</au><au>MUBAGWA, Kanigula</au><au>SIPIDO, Karin R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reduced synchrony of Ca2+ release with loss of T-tubules: a comparison to Ca2+ release in human failing cardiomyocytes</atitle><jtitle>Cardiovascular research</jtitle><addtitle>Cardiovasc Res</addtitle><date>2004-04-01</date><risdate>2004</risdate><volume>62</volume><issue>1</issue><spage>63</spage><epage>73</epage><pages>63-73</pages><issn>0008-6363</issn><eissn>1755-3245</eissn><coden>CVREAU</coden><abstract>During cardiac excitation-contraction coupling, Ca2+ release from the sarcoplasmic reticulum (SR) occurs at the junctional complex with the T-tubules, containing the L-type Ca2+ channels. A partial loss of T-tubules has been described in myocytes from failing canine and human hearts. We examined how graded reduction of T-tubule density would affect the synchrony of Ca2+ release.
Adult pig ventricular myocytes were isolated and cultured for 24 and 72 h. T-tubules, visualized with di-8-ANEPPS, and [Ca2+]i transients (Fluo-3) were recorded during confocal line scan imaging.
Cultured cardiomyocytes exhibited a progressive reduction in T-tubule density. [Ca2+]i transients showed small areas of delayed Ca2+ release which gradually increased in number and size with loss of T-tubules. Local [Ca2+]i transients in the delayed regions were reduced. Due to these changes, loss of T-tubules resulted in an overall slowing of the rise of [Ca2+] along the entire line scan and transient magnitude tended to be reduced, but there was no change in SR Ca2+ content. Human myocytes isolated from failing hearts had a T-tubule density comparable to that of freshly isolated pig myocytes. The size, but not the number, of delayed release areas tended to be larger. The overall rate of rise of [Ca2+]i was significantly faster than in pig myocytes with low T-tubule density.
Loss of T-tubules reduces the synchrony of SR Ca2+ release. This could contribute to reduced efficiency of excitation-contraction coupling in heart failure, though dyssynchrony in human failing cells appears to be modest.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>15023553</pmid><doi>10.1016/j.cardiores.2003.12.031</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Biological and medical sciences Calcium - metabolism Cardiology. Vascular system Cells, Cultured Electrophysiology Heart Heart Failure - metabolism Heart Failure - pathology Heart failure, cardiogenic pulmonary edema, cardiac enlargement Humans Image Processing, Computer-Assisted Medical sciences Microscopy, Confocal Myocytes, Cardiac - metabolism Myocytes, Cardiac - ultrastructure Sarcoplasmic Reticulum - ultrastructure Swine |
title | Reduced synchrony of Ca2+ release with loss of T-tubules: a comparison to Ca2+ release in human failing cardiomyocytes |
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