Increased availability and open probability of single L-type calcium channels from failing compared with nonfailing human ventricle
The role of the L-type calcium channel in human heart failure is unclear, on the basis of previous whole-cell recordings. We investigated the properties of L-type calcium channels in left ventricular myocytes isolated from nonfailing donor hearts (n= 16 cells) or failing hearts of transplant recipie...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 1998-09, Vol.98 (10), p.969-976 |
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| container_title | Circulation (New York, N.Y.) |
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| creator | SCHRÖDER, F HANDROCK, R BEUCKELMANN, D. J HIRT, S HULLIN, R PRIEBE, L SCHWINGER, R. H. G WEIL, J HERZIG, S |
| description | The role of the L-type calcium channel in human heart failure is unclear, on the basis of previous whole-cell recordings.
We investigated the properties of L-type calcium channels in left ventricular myocytes isolated from nonfailing donor hearts (n= 16 cells) or failing hearts of transplant recipients with dilated (n=9) or ischemic (n=7) cardiomyopathy. The single-channel recording technique was used (70 mmol/L Ba2+). Peak average currents were significantly enhanced in heart failure (38.2+/-9.3 fA) versus nonfailing control hearts (13.2+/-4.5 fA, P=0.02) because of an elevation of channel availability (55.9+/-6.7% versus 26.4+/-5.3%, P=0.001) and open probability within active sweeps (7.36+/-1.51% versus 3.18+/-1.33%, P=0.04). These differences closely resembled the effects of a cAMP-dependent stimulation with 8-Br-cAMP (n= 11). Kinetic analysis of the slow gating shows that channels from failing hearts remain available for a longer time, suggesting a defect in the dephosphorylation. Indeed, the phosphatase inhibitor okadaic acid was unable to stimulate channel activity in myocytes from failing hearts (n=5). Expression of calcium channel subunits was measured by Northern blot analysis. Expression of alpha1c- and beta-subunits was unaltered. Whole-cell current measurements did not reveal an increase of current density in heart failure.
Individual L-type calcium channels are fundamentally affected in severe human heart failure. This is probably important for the impairment of cardiac excitation-contraction coupling. |
| doi_str_mv | 10.1161/01.CIR.98.10.969 |
| format | Article |
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We investigated the properties of L-type calcium channels in left ventricular myocytes isolated from nonfailing donor hearts (n= 16 cells) or failing hearts of transplant recipients with dilated (n=9) or ischemic (n=7) cardiomyopathy. The single-channel recording technique was used (70 mmol/L Ba2+). Peak average currents were significantly enhanced in heart failure (38.2+/-9.3 fA) versus nonfailing control hearts (13.2+/-4.5 fA, P=0.02) because of an elevation of channel availability (55.9+/-6.7% versus 26.4+/-5.3%, P=0.001) and open probability within active sweeps (7.36+/-1.51% versus 3.18+/-1.33%, P=0.04). These differences closely resembled the effects of a cAMP-dependent stimulation with 8-Br-cAMP (n= 11). Kinetic analysis of the slow gating shows that channels from failing hearts remain available for a longer time, suggesting a defect in the dephosphorylation. Indeed, the phosphatase inhibitor okadaic acid was unable to stimulate channel activity in myocytes from failing hearts (n=5). Expression of calcium channel subunits was measured by Northern blot analysis. Expression of alpha1c- and beta-subunits was unaltered. Whole-cell current measurements did not reveal an increase of current density in heart failure.
Individual L-type calcium channels are fundamentally affected in severe human heart failure. This is probably important for the impairment of cardiac excitation-contraction coupling.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.CIR.98.10.969</identifier><identifier>PMID: 9737516</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>8-Bromo Cyclic Adenosine Monophosphate - pharmacology ; Biological and medical sciences ; Calcium Channels - physiology ; Calcium Channels, L-Type ; Cardiology. Vascular system ; Cardiomyopathies - physiopathology ; Cardiomyopathy, Dilated - physiopathology ; Cells, Cultured ; Cyclic AMP - physiology ; Heart ; Heart - physiology ; Heart - physiopathology ; Heart failure, cardiogenic pulmonary edema, cardiac enlargement ; Heart Ventricles ; Humans ; Ion Channel Gating ; Kinetics ; Medical sciences ; Membrane Potentials ; Myocardial Ischemia - physiopathology ; Probability ; Reference Values ; Time Factors</subject><ispartof>Circulation (New York, N.Y.), 1998-09, Vol.98 (10), p.969-976</ispartof><rights>1998 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Sep 8, 1998</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c480t-a58c74341c0ed0add10b4e05cfc0fcd5ff8238f4f94922d4922b4088204e5ee83</citedby><cites>FETCH-LOGICAL-c480t-a58c74341c0ed0add10b4e05cfc0fcd5ff8238f4f94922d4922b4088204e5ee83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3687,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2371696$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9737516$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SCHRÖDER, F</creatorcontrib><creatorcontrib>HANDROCK, R</creatorcontrib><creatorcontrib>BEUCKELMANN, D. J</creatorcontrib><creatorcontrib>HIRT, S</creatorcontrib><creatorcontrib>HULLIN, R</creatorcontrib><creatorcontrib>PRIEBE, L</creatorcontrib><creatorcontrib>SCHWINGER, R. H. G</creatorcontrib><creatorcontrib>WEIL, J</creatorcontrib><creatorcontrib>HERZIG, S</creatorcontrib><title>Increased availability and open probability of single L-type calcium channels from failing compared with nonfailing human ventricle</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>The role of the L-type calcium channel in human heart failure is unclear, on the basis of previous whole-cell recordings.
We investigated the properties of L-type calcium channels in left ventricular myocytes isolated from nonfailing donor hearts (n= 16 cells) or failing hearts of transplant recipients with dilated (n=9) or ischemic (n=7) cardiomyopathy. The single-channel recording technique was used (70 mmol/L Ba2+). Peak average currents were significantly enhanced in heart failure (38.2+/-9.3 fA) versus nonfailing control hearts (13.2+/-4.5 fA, P=0.02) because of an elevation of channel availability (55.9+/-6.7% versus 26.4+/-5.3%, P=0.001) and open probability within active sweeps (7.36+/-1.51% versus 3.18+/-1.33%, P=0.04). These differences closely resembled the effects of a cAMP-dependent stimulation with 8-Br-cAMP (n= 11). Kinetic analysis of the slow gating shows that channels from failing hearts remain available for a longer time, suggesting a defect in the dephosphorylation. Indeed, the phosphatase inhibitor okadaic acid was unable to stimulate channel activity in myocytes from failing hearts (n=5). Expression of calcium channel subunits was measured by Northern blot analysis. Expression of alpha1c- and beta-subunits was unaltered. Whole-cell current measurements did not reveal an increase of current density in heart failure.
Individual L-type calcium channels are fundamentally affected in severe human heart failure. This is probably important for the impairment of cardiac excitation-contraction coupling.</description><subject>8-Bromo Cyclic Adenosine Monophosphate - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Calcium Channels - physiology</subject><subject>Calcium Channels, L-Type</subject><subject>Cardiology. Vascular system</subject><subject>Cardiomyopathies - physiopathology</subject><subject>Cardiomyopathy, Dilated - physiopathology</subject><subject>Cells, Cultured</subject><subject>Cyclic AMP - physiology</subject><subject>Heart</subject><subject>Heart - physiology</subject><subject>Heart - physiopathology</subject><subject>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</subject><subject>Heart Ventricles</subject><subject>Humans</subject><subject>Ion Channel Gating</subject><subject>Kinetics</subject><subject>Medical sciences</subject><subject>Membrane Potentials</subject><subject>Myocardial Ischemia - physiopathology</subject><subject>Probability</subject><subject>Reference Values</subject><subject>Time Factors</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdUU2LFDEUDKKs4-jdixBEvPWYz-7kKIMfAwOC6Dmk0y9OlnS6TbpX5uwfN8PO7sFLHqmqV8l7hdBrSnaUtvQDobv94ftOq11FdKufoA2VTDRCcv0UbQghuuk4Y8_Ri1Ju67XlnbxBN7qrlbYb9PeQXAZbYMD2zoZo-xDDcsY2DXiaIeE5T_0DOHlcQvoVAR-b5TwDdja6sI7YnWxKEAv2eRqxrz5Vht00zjZX5z9hOeE0pQfitI424TtISw4uwkv0zNtY4NW1btHPz59-7L82x29fDvuPx8YJRZbGSuU6wQV1BAZih4GSXgCRzjvi3SC9V4wrL7wWmrHhcvSCKMWIAAmg-Ba9v_etM_1eoSxmDMVBjDbBtBbTcU2kbmUVvv1PeDutOdW_GUZZx7SoL20RuRe5PJWSwZs5h9Hms6HEXMIxhJoajtHqgtRwasubq-_ajzA8NlzTqPy7K29LXa3PNrlQHmWMd7TVLf8Hda6ZJw</recordid><startdate>19980908</startdate><enddate>19980908</enddate><creator>SCHRÖDER, F</creator><creator>HANDROCK, R</creator><creator>BEUCKELMANN, D. J</creator><creator>HIRT, S</creator><creator>HULLIN, R</creator><creator>PRIEBE, L</creator><creator>SCHWINGER, R. H. G</creator><creator>WEIL, J</creator><creator>HERZIG, S</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>19980908</creationdate><title>Increased availability and open probability of single L-type calcium channels from failing compared with nonfailing human ventricle</title><author>SCHRÖDER, F ; HANDROCK, R ; BEUCKELMANN, D. J ; HIRT, S ; HULLIN, R ; PRIEBE, L ; SCHWINGER, R. H. G ; WEIL, J ; HERZIG, S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c480t-a58c74341c0ed0add10b4e05cfc0fcd5ff8238f4f94922d4922b4088204e5ee83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>8-Bromo Cyclic Adenosine Monophosphate - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Calcium Channels - physiology</topic><topic>Calcium Channels, L-Type</topic><topic>Cardiology. Vascular system</topic><topic>Cardiomyopathies - physiopathology</topic><topic>Cardiomyopathy, Dilated - physiopathology</topic><topic>Cells, Cultured</topic><topic>Cyclic AMP - physiology</topic><topic>Heart</topic><topic>Heart - physiology</topic><topic>Heart - physiopathology</topic><topic>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</topic><topic>Heart Ventricles</topic><topic>Humans</topic><topic>Ion Channel Gating</topic><topic>Kinetics</topic><topic>Medical sciences</topic><topic>Membrane Potentials</topic><topic>Myocardial Ischemia - physiopathology</topic><topic>Probability</topic><topic>Reference Values</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SCHRÖDER, F</creatorcontrib><creatorcontrib>HANDROCK, R</creatorcontrib><creatorcontrib>BEUCKELMANN, D. J</creatorcontrib><creatorcontrib>HIRT, S</creatorcontrib><creatorcontrib>HULLIN, R</creatorcontrib><creatorcontrib>PRIEBE, L</creatorcontrib><creatorcontrib>SCHWINGER, R. H. G</creatorcontrib><creatorcontrib>WEIL, J</creatorcontrib><creatorcontrib>HERZIG, S</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>SCHRÖDER, F</au><au>HANDROCK, R</au><au>BEUCKELMANN, D. J</au><au>HIRT, S</au><au>HULLIN, R</au><au>PRIEBE, L</au><au>SCHWINGER, R. H. G</au><au>WEIL, J</au><au>HERZIG, S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased availability and open probability of single L-type calcium channels from failing compared with nonfailing human ventricle</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>1998-09-08</date><risdate>1998</risdate><volume>98</volume><issue>10</issue><spage>969</spage><epage>976</epage><pages>969-976</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>The role of the L-type calcium channel in human heart failure is unclear, on the basis of previous whole-cell recordings.
We investigated the properties of L-type calcium channels in left ventricular myocytes isolated from nonfailing donor hearts (n= 16 cells) or failing hearts of transplant recipients with dilated (n=9) or ischemic (n=7) cardiomyopathy. The single-channel recording technique was used (70 mmol/L Ba2+). Peak average currents were significantly enhanced in heart failure (38.2+/-9.3 fA) versus nonfailing control hearts (13.2+/-4.5 fA, P=0.02) because of an elevation of channel availability (55.9+/-6.7% versus 26.4+/-5.3%, P=0.001) and open probability within active sweeps (7.36+/-1.51% versus 3.18+/-1.33%, P=0.04). These differences closely resembled the effects of a cAMP-dependent stimulation with 8-Br-cAMP (n= 11). Kinetic analysis of the slow gating shows that channels from failing hearts remain available for a longer time, suggesting a defect in the dephosphorylation. Indeed, the phosphatase inhibitor okadaic acid was unable to stimulate channel activity in myocytes from failing hearts (n=5). Expression of calcium channel subunits was measured by Northern blot analysis. Expression of alpha1c- and beta-subunits was unaltered. Whole-cell current measurements did not reveal an increase of current density in heart failure.
Individual L-type calcium channels are fundamentally affected in severe human heart failure. This is probably important for the impairment of cardiac excitation-contraction coupling.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>9737516</pmid><doi>10.1161/01.CIR.98.10.969</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Heart Association Journals; Journals@Ovid Complete; EZB-FREE-00999 freely available EZB journals |
| subjects | 8-Bromo Cyclic Adenosine Monophosphate - pharmacology Biological and medical sciences Calcium Channels - physiology Calcium Channels, L-Type Cardiology. Vascular system Cardiomyopathies - physiopathology Cardiomyopathy, Dilated - physiopathology Cells, Cultured Cyclic AMP - physiology Heart Heart - physiology Heart - physiopathology Heart failure, cardiogenic pulmonary edema, cardiac enlargement Heart Ventricles Humans Ion Channel Gating Kinetics Medical sciences Membrane Potentials Myocardial Ischemia - physiopathology Probability Reference Values Time Factors |
| title | Increased availability and open probability of single L-type calcium channels from failing compared with nonfailing human ventricle |
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