A Subpopulation of Rat Muscle Fibers Maintains an Assessable Excitation-Contraction Coupling Mechanism After Long-Standing Denervation Despite Lost Contractility
To define the time course and potential effects of electrical stimulation on permanently denervated muscle, we evaluated excitation-contraction coupling (ECC) of rat leg muscles during progression to long-term denervation by ultrastructural analysis, specific binding to dihydropyridine receptors, ry...
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creator | Squecco, Roberta Carraro, Ugo Kern, Helmut Pond, Amber Adami, Nicoletta Biral, Donatella Vindigni, Vincenzo Boncompagni, Simona Pietrangelo, Tiziana Bosco, Gerardo Fanò, Giorgio Marini, Marina Abruzzo, Provvidenza M Germinario, Elena Danieli-Betto, Daniela Protasi, Feliciano Francini, Fabio Zampieri, Sandra |
description | To define the time course and potential effects of electrical stimulation on permanently denervated muscle, we evaluated excitation-contraction coupling (ECC) of rat leg muscles during progression to long-term denervation by ultrastructural analysis, specific binding to dihydropyridine receptors, ryanodine receptor 1 (RYR-1), Ca channels and extrusion Ca pumps, gene transcription and translation of Ca-handling proteins, and in vitro mechanical properties andelectrophysiological analyses of sarcolemmal passive properties and L-type Ca current (ICa) parameters. We found that in response to long-term denervation1) isolated muscle that is unable to twitch in vitro by electrical stimulation has very small myofibers but may show a slow caffeine contracture; 2) only roughly half of the muscle fibers with "voltage-dependent Ca channel activity" are able to contract; 3) the ECC mechanisms are still present and, in part, functional; 4)ECC-related gene expression is upregulated; and 5) at any time point, there are muscle fibers that are more resistant than others to denervation atrophy and disorganization of the ECC apparatus. These results support the hypothesis that prolonged "resting" [Ca] may drive progression of muscle atrophy to degeneration and that electrical stimulation-induced [Ca] modulation may mimic the lostnerve influence, playing a key role in modifying the gene expression of denervated muscle. Hence, these data provide a potential molecular explanation for the muscle recovery that occurs in responseto rehabilitation strategies developed based on empirical clinical observations. |
doi_str_mv | 10.1097/NEN.0b013e3181c18416 |
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We found that in response to long-term denervation1) isolated muscle that is unable to twitch in vitro by electrical stimulation has very small myofibers but may show a slow caffeine contracture; 2) only roughly half of the muscle fibers with "voltage-dependent Ca channel activity" are able to contract; 3) the ECC mechanisms are still present and, in part, functional; 4)ECC-related gene expression is upregulated; and 5) at any time point, there are muscle fibers that are more resistant than others to denervation atrophy and disorganization of the ECC apparatus. These results support the hypothesis that prolonged "resting" [Ca] may drive progression of muscle atrophy to degeneration and that electrical stimulation-induced [Ca] modulation may mimic the lostnerve influence, playing a key role in modifying the gene expression of denervated muscle. Hence, these data provide a potential molecular explanation for the muscle recovery that occurs in responseto rehabilitation strategies developed based on empirical clinical observations.</description><identifier>ISSN: 0022-3069</identifier><identifier>EISSN: 1554-6578</identifier><identifier>DOI: 10.1097/NEN.0b013e3181c18416</identifier><identifier>PMID: 19915489</identifier><identifier>CODEN: JNENAD</identifier><language>eng</language><publisher>Hagerstown, MD: American Association of Neuropathologists, Inc</publisher><subject>Animals ; Biological and medical sciences ; Calcium Channels - physiology ; Gene Expression ; Male ; Medical sciences ; Membrane Potentials - physiology ; Microscopy, Electron, Transmission ; Muscle Contraction - physiology ; Muscle Denervation - adverse effects ; Muscle Proteins - biosynthesis ; Muscle Proteins - genetics ; Muscle, Skeletal - physiology ; Muscular Atrophy - physiopathology ; Neurology ; Patch-Clamp Techniques ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction</subject><ispartof>Journal of neuropathology and experimental neurology, 2009-12, Vol.68 (12), p.1256-1268</ispartof><rights>2009 American Association of Neuropathologists, Inc</rights><rights>2015 INIST-CNRS</rights><rights>Copyright Lippincott Williams & Wilkins Dec 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5416-475e3642d686836cc54410c711415db7d52ed1eefc8a2002e0e5b56232dc83d03</citedby><cites>FETCH-LOGICAL-c5416-475e3642d686836cc54410c711415db7d52ed1eefc8a2002e0e5b56232dc83d03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22209018$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19915489$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Squecco, Roberta</creatorcontrib><creatorcontrib>Carraro, Ugo</creatorcontrib><creatorcontrib>Kern, Helmut</creatorcontrib><creatorcontrib>Pond, Amber</creatorcontrib><creatorcontrib>Adami, Nicoletta</creatorcontrib><creatorcontrib>Biral, Donatella</creatorcontrib><creatorcontrib>Vindigni, Vincenzo</creatorcontrib><creatorcontrib>Boncompagni, Simona</creatorcontrib><creatorcontrib>Pietrangelo, Tiziana</creatorcontrib><creatorcontrib>Bosco, Gerardo</creatorcontrib><creatorcontrib>Fanò, Giorgio</creatorcontrib><creatorcontrib>Marini, Marina</creatorcontrib><creatorcontrib>Abruzzo, Provvidenza M</creatorcontrib><creatorcontrib>Germinario, Elena</creatorcontrib><creatorcontrib>Danieli-Betto, Daniela</creatorcontrib><creatorcontrib>Protasi, Feliciano</creatorcontrib><creatorcontrib>Francini, Fabio</creatorcontrib><creatorcontrib>Zampieri, Sandra</creatorcontrib><title>A Subpopulation of Rat Muscle Fibers Maintains an Assessable Excitation-Contraction Coupling Mechanism After Long-Standing Denervation Despite Lost Contractility</title><title>Journal of neuropathology and experimental neurology</title><addtitle>J Neuropathol Exp Neurol</addtitle><description>To define the time course and potential effects of electrical stimulation on permanently denervated muscle, we evaluated excitation-contraction coupling (ECC) of rat leg muscles during progression to long-term denervation by ultrastructural analysis, specific binding to dihydropyridine receptors, ryanodine receptor 1 (RYR-1), Ca channels and extrusion Ca pumps, gene transcription and translation of Ca-handling proteins, and in vitro mechanical properties andelectrophysiological analyses of sarcolemmal passive properties and L-type Ca current (ICa) parameters. We found that in response to long-term denervation1) isolated muscle that is unable to twitch in vitro by electrical stimulation has very small myofibers but may show a slow caffeine contracture; 2) only roughly half of the muscle fibers with "voltage-dependent Ca channel activity" are able to contract; 3) the ECC mechanisms are still present and, in part, functional; 4)ECC-related gene expression is upregulated; and 5) at any time point, there are muscle fibers that are more resistant than others to denervation atrophy and disorganization of the ECC apparatus. These results support the hypothesis that prolonged "resting" [Ca] may drive progression of muscle atrophy to degeneration and that electrical stimulation-induced [Ca] modulation may mimic the lostnerve influence, playing a key role in modifying the gene expression of denervated muscle. Hence, these data provide a potential molecular explanation for the muscle recovery that occurs in responseto rehabilitation strategies developed based on empirical clinical observations.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Calcium Channels - physiology</subject><subject>Gene Expression</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membrane Potentials - physiology</subject><subject>Microscopy, Electron, Transmission</subject><subject>Muscle Contraction - physiology</subject><subject>Muscle Denervation - adverse effects</subject><subject>Muscle Proteins - biosynthesis</subject><subject>Muscle Proteins - genetics</subject><subject>Muscle, Skeletal - physiology</subject><subject>Muscular Atrophy - physiopathology</subject><subject>Neurology</subject><subject>Patch-Clamp Techniques</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><issn>0022-3069</issn><issn>1554-6578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFktFuFCEUhonR2G31DYwhJsarqcDADHO52W7VZLcmVq8nDHOmS2VhCoy1j9M3le1uatILvSAknO__D4cfhN5QckpJU3-8WF6cko7QEkoqqaaS0-oZmlEheFGJWj5HM0IYK0pSNUfoOMZrQkhDGv4SHdGmoYLLZobu5_hy6kY_TlYl4x32A_6mEl5PUVvA56aDEPFaGZfyilg5PI8RYlRdLi9_a5MedMXCuxSUfvBY-Gm0xl3hNeiNciZu8XxIEPDKu6viMinX76pn4CD82rc9gziaBJmICT96WZPuXqEXg7IRXh_2E_TjfPl98blYff30ZTFfFVrkyQteCygrzvpKVrKsdD7llOiaUk5F39W9YNBTgEFLxfLDAAHRiYqVrNey7El5gj7sfcfgbyaIqd2aqMFa5cBPsa05r4kkQvyfLHNLIemOfPeEvPZTcHmMlrGmJpUgZYb4HtLBxxhgaMdgtirctZS0u6jbHHX7NOose3vwnrot9H9Fh2wz8P4AqKiVHYJy2sRHjjGWvwOVmZN77tbbHFL8aadbCO0GlE2bf9_hD-HFxSY</recordid><startdate>200912</startdate><enddate>200912</enddate><creator>Squecco, Roberta</creator><creator>Carraro, Ugo</creator><creator>Kern, Helmut</creator><creator>Pond, Amber</creator><creator>Adami, Nicoletta</creator><creator>Biral, Donatella</creator><creator>Vindigni, Vincenzo</creator><creator>Boncompagni, Simona</creator><creator>Pietrangelo, Tiziana</creator><creator>Bosco, Gerardo</creator><creator>Fanò, Giorgio</creator><creator>Marini, Marina</creator><creator>Abruzzo, Provvidenza M</creator><creator>Germinario, Elena</creator><creator>Danieli-Betto, Daniela</creator><creator>Protasi, Feliciano</creator><creator>Francini, Fabio</creator><creator>Zampieri, Sandra</creator><general>American Association of Neuropathologists, Inc</general><general>Lippincott Williams & Wilkins</general><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope><scope>7QP</scope><scope>7TK</scope></search><sort><creationdate>200912</creationdate><title>A Subpopulation of Rat Muscle Fibers Maintains an Assessable Excitation-Contraction Coupling Mechanism After Long-Standing Denervation Despite Lost Contractility</title><author>Squecco, Roberta ; Carraro, Ugo ; Kern, Helmut ; Pond, Amber ; Adami, Nicoletta ; Biral, Donatella ; Vindigni, Vincenzo ; Boncompagni, Simona ; Pietrangelo, Tiziana ; Bosco, Gerardo ; Fanò, Giorgio ; Marini, Marina ; Abruzzo, Provvidenza M ; Germinario, Elena ; Danieli-Betto, Daniela ; Protasi, Feliciano ; Francini, Fabio ; Zampieri, Sandra</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5416-475e3642d686836cc54410c711415db7d52ed1eefc8a2002e0e5b56232dc83d03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Calcium Channels - physiology</topic><topic>Gene Expression</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Membrane Potentials - physiology</topic><topic>Microscopy, Electron, Transmission</topic><topic>Muscle Contraction - physiology</topic><topic>Muscle Denervation - adverse effects</topic><topic>Muscle Proteins - biosynthesis</topic><topic>Muscle Proteins - genetics</topic><topic>Muscle, Skeletal - physiology</topic><topic>Muscular Atrophy - physiopathology</topic><topic>Neurology</topic><topic>Patch-Clamp Techniques</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Squecco, Roberta</creatorcontrib><creatorcontrib>Carraro, Ugo</creatorcontrib><creatorcontrib>Kern, Helmut</creatorcontrib><creatorcontrib>Pond, Amber</creatorcontrib><creatorcontrib>Adami, Nicoletta</creatorcontrib><creatorcontrib>Biral, Donatella</creatorcontrib><creatorcontrib>Vindigni, Vincenzo</creatorcontrib><creatorcontrib>Boncompagni, Simona</creatorcontrib><creatorcontrib>Pietrangelo, Tiziana</creatorcontrib><creatorcontrib>Bosco, Gerardo</creatorcontrib><creatorcontrib>Fanò, Giorgio</creatorcontrib><creatorcontrib>Marini, Marina</creatorcontrib><creatorcontrib>Abruzzo, Provvidenza M</creatorcontrib><creatorcontrib>Germinario, Elena</creatorcontrib><creatorcontrib>Danieli-Betto, Daniela</creatorcontrib><creatorcontrib>Protasi, Feliciano</creatorcontrib><creatorcontrib>Francini, Fabio</creatorcontrib><creatorcontrib>Zampieri, Sandra</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 Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><jtitle>Journal of neuropathology and experimental neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Squecco, Roberta</au><au>Carraro, Ugo</au><au>Kern, Helmut</au><au>Pond, Amber</au><au>Adami, Nicoletta</au><au>Biral, Donatella</au><au>Vindigni, Vincenzo</au><au>Boncompagni, Simona</au><au>Pietrangelo, Tiziana</au><au>Bosco, Gerardo</au><au>Fanò, Giorgio</au><au>Marini, Marina</au><au>Abruzzo, Provvidenza M</au><au>Germinario, Elena</au><au>Danieli-Betto, Daniela</au><au>Protasi, Feliciano</au><au>Francini, Fabio</au><au>Zampieri, Sandra</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Subpopulation of Rat Muscle Fibers Maintains an Assessable Excitation-Contraction Coupling Mechanism After Long-Standing Denervation Despite Lost Contractility</atitle><jtitle>Journal of neuropathology and experimental neurology</jtitle><addtitle>J Neuropathol Exp Neurol</addtitle><date>2009-12</date><risdate>2009</risdate><volume>68</volume><issue>12</issue><spage>1256</spage><epage>1268</epage><pages>1256-1268</pages><issn>0022-3069</issn><eissn>1554-6578</eissn><coden>JNENAD</coden><abstract>To define the time course and potential effects of electrical stimulation on permanently denervated muscle, we evaluated excitation-contraction coupling (ECC) of rat leg muscles during progression to long-term denervation by ultrastructural analysis, specific binding to dihydropyridine receptors, ryanodine receptor 1 (RYR-1), Ca channels and extrusion Ca pumps, gene transcription and translation of Ca-handling proteins, and in vitro mechanical properties andelectrophysiological analyses of sarcolemmal passive properties and L-type Ca current (ICa) parameters. We found that in response to long-term denervation1) isolated muscle that is unable to twitch in vitro by electrical stimulation has very small myofibers but may show a slow caffeine contracture; 2) only roughly half of the muscle fibers with "voltage-dependent Ca channel activity" are able to contract; 3) the ECC mechanisms are still present and, in part, functional; 4)ECC-related gene expression is upregulated; and 5) at any time point, there are muscle fibers that are more resistant than others to denervation atrophy and disorganization of the ECC apparatus. These results support the hypothesis that prolonged "resting" [Ca] may drive progression of muscle atrophy to degeneration and that electrical stimulation-induced [Ca] modulation may mimic the lostnerve influence, playing a key role in modifying the gene expression of denervated muscle. Hence, these data provide a potential molecular explanation for the muscle recovery that occurs in responseto rehabilitation strategies developed based on empirical clinical observations.</abstract><cop>Hagerstown, MD</cop><pub>American Association of Neuropathologists, Inc</pub><pmid>19915489</pmid><doi>10.1097/NEN.0b013e3181c18416</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Biological and medical sciences Calcium Channels - physiology Gene Expression Male Medical sciences Membrane Potentials - physiology Microscopy, Electron, Transmission Muscle Contraction - physiology Muscle Denervation - adverse effects Muscle Proteins - biosynthesis Muscle Proteins - genetics Muscle, Skeletal - physiology Muscular Atrophy - physiopathology Neurology Patch-Clamp Techniques Rats Rats, Wistar Reverse Transcriptase Polymerase Chain Reaction |
title | A Subpopulation of Rat Muscle Fibers Maintains an Assessable Excitation-Contraction Coupling Mechanism After Long-Standing Denervation Despite Lost Contractility |
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