Ionic mechanism of delayed afterdepolarizations in ventricular cells isolated from human end-stage failing hearts
Animal studies have shown that the Ca(2+)-activated Cl(-) current (I(Cl(Ca))) and the Na(+)/Ca(2+) exchange current (I(Na/Ca)) contribute to the transient inward current (I(ti)). I(ti) is responsible for the proarrhythmic delayed afterdepolarizations (DADs). We investigated the ionic mechanism of I(...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2001-11, Vol.104 (22), p.2728-2733 |
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| creator | VERKERK, Arie O VELDKAMP, Marieke W BAARTSCHEER, Antonius SCHUMACHER, Cees A KLÖPPING, Corinne VAN GINNEKEN, Antoni C. G RAVESLOOT, Jan H |
| description | Animal studies have shown that the Ca(2+)-activated Cl(-) current (I(Cl(Ca))) and the Na(+)/Ca(2+) exchange current (I(Na/Ca)) contribute to the transient inward current (I(ti)). I(ti) is responsible for the proarrhythmic delayed afterdepolarizations (DADs). We investigated the ionic mechanism of I(ti) and DADs in human cardiac cells.
Human ventricular cells were enzymatically isolated from explanted hearts of patients with end-stage heart failure and studied with patch-clamp methodology. I(ti)s were elicited in the presence of 1 micromol/L norepinephrine by trains of repetitive depolarizations from -80 to +50 mV. DADs were induced in the presence of 1 micromol/L norepinephrine at a stimulus frequency of 1 Hz. I(ti) currents were inwardly directed over the voltage range between -110 and + 50 mV. Neither the Cl(-) channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid nor changes in [Cl(-)](i) affected I(ti) or DAD amplitude. This excludes an important role for I(Cl(Ca)). Blockade of Na(+)/Ca(2+) exchange by substitution of all extracellular Na(+) by Li(+), conversely, completely inhibited I(ti). In rabbit, I(Cl(Ca)) density in ventricular cells isolated from control hearts did not differ significantly from that in ventricular cells isolated from failing hearts.
In contrast to many animal species, I(ti) and DADs in human ventricular cells from failing hearts consist only of I(Na/Ca). In rabbits, heart failure per se does not alter I(Cl(Ca)) density, suggesting that I(Cl(Ca)) may also be absent during DADs in nonfailing human ventricular cells. |
| doi_str_mv | 10.1161/hc4701.099577 |
| format | Article |
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Human ventricular cells were enzymatically isolated from explanted hearts of patients with end-stage heart failure and studied with patch-clamp methodology. I(ti)s were elicited in the presence of 1 micromol/L norepinephrine by trains of repetitive depolarizations from -80 to +50 mV. DADs were induced in the presence of 1 micromol/L norepinephrine at a stimulus frequency of 1 Hz. I(ti) currents were inwardly directed over the voltage range between -110 and + 50 mV. Neither the Cl(-) channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid nor changes in [Cl(-)](i) affected I(ti) or DAD amplitude. This excludes an important role for I(Cl(Ca)). Blockade of Na(+)/Ca(2+) exchange by substitution of all extracellular Na(+) by Li(+), conversely, completely inhibited I(ti). In rabbit, I(Cl(Ca)) density in ventricular cells isolated from control hearts did not differ significantly from that in ventricular cells isolated from failing hearts.
In contrast to many animal species, I(ti) and DADs in human ventricular cells from failing hearts consist only of I(Na/Ca). In rabbits, heart failure per se does not alter I(Cl(Ca)) density, suggesting that I(Cl(Ca)) may also be absent during DADs in nonfailing human ventricular cells.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/hc4701.099577</identifier><identifier>PMID: 11723027</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid - pharmacology ; Adult ; Animals ; Biological and medical sciences ; Calcium - metabolism ; Cardiology. Vascular system ; Cell Separation ; Chloride Channels - antagonists & inhibitors ; Disease Models, Animal ; Electric Stimulation ; Female ; Heart ; Heart Failure - pathology ; Heart Failure - physiopathology ; Heart failure, cardiogenic pulmonary edema, cardiac enlargement ; Heart Ventricles - drug effects ; Heart Ventricles - pathology ; Heart Ventricles - physiopathology ; Humans ; In Vitro Techniques ; Lithium - pharmacology ; Male ; Medical sciences ; Membrane Potentials - drug effects ; Middle Aged ; Norepinephrine - pharmacology ; Patch-Clamp Techniques ; Rabbits ; Sodium-Calcium Exchanger - antagonists & inhibitors</subject><ispartof>Circulation (New York, N.Y.), 2001-11, Vol.104 (22), p.2728-2733</ispartof><rights>2002 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Nov 27, 2001</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c494t-ec535821d18af992bf44b70240bff5fec62b14dd9152ef78cc1ab139312160003</citedby><cites>FETCH-LOGICAL-c494t-ec535821d18af992bf44b70240bff5fec62b14dd9152ef78cc1ab139312160003</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3674,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14113536$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11723027$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>VERKERK, Arie O</creatorcontrib><creatorcontrib>VELDKAMP, Marieke W</creatorcontrib><creatorcontrib>BAARTSCHEER, Antonius</creatorcontrib><creatorcontrib>SCHUMACHER, Cees A</creatorcontrib><creatorcontrib>KLÖPPING, Corinne</creatorcontrib><creatorcontrib>VAN GINNEKEN, Antoni C. G</creatorcontrib><creatorcontrib>RAVESLOOT, Jan H</creatorcontrib><title>Ionic mechanism of delayed afterdepolarizations in ventricular cells isolated from human end-stage failing hearts</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Animal studies have shown that the Ca(2+)-activated Cl(-) current (I(Cl(Ca))) and the Na(+)/Ca(2+) exchange current (I(Na/Ca)) contribute to the transient inward current (I(ti)). I(ti) is responsible for the proarrhythmic delayed afterdepolarizations (DADs). We investigated the ionic mechanism of I(ti) and DADs in human cardiac cells.
Human ventricular cells were enzymatically isolated from explanted hearts of patients with end-stage heart failure and studied with patch-clamp methodology. I(ti)s were elicited in the presence of 1 micromol/L norepinephrine by trains of repetitive depolarizations from -80 to +50 mV. DADs were induced in the presence of 1 micromol/L norepinephrine at a stimulus frequency of 1 Hz. I(ti) currents were inwardly directed over the voltage range between -110 and + 50 mV. Neither the Cl(-) channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid nor changes in [Cl(-)](i) affected I(ti) or DAD amplitude. This excludes an important role for I(Cl(Ca)). Blockade of Na(+)/Ca(2+) exchange by substitution of all extracellular Na(+) by Li(+), conversely, completely inhibited I(ti). In rabbit, I(Cl(Ca)) density in ventricular cells isolated from control hearts did not differ significantly from that in ventricular cells isolated from failing hearts.
In contrast to many animal species, I(ti) and DADs in human ventricular cells from failing hearts consist only of I(Na/Ca). In rabbits, heart failure per se does not alter I(Cl(Ca)) density, suggesting that I(Cl(Ca)) may also be absent during DADs in nonfailing human ventricular cells.</description><subject>4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid - pharmacology</subject><subject>Adult</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Calcium - metabolism</subject><subject>Cardiology. Vascular system</subject><subject>Cell Separation</subject><subject>Chloride Channels - antagonists & inhibitors</subject><subject>Disease Models, Animal</subject><subject>Electric Stimulation</subject><subject>Female</subject><subject>Heart</subject><subject>Heart Failure - pathology</subject><subject>Heart Failure - physiopathology</subject><subject>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</subject><subject>Heart Ventricles - drug effects</subject><subject>Heart Ventricles - pathology</subject><subject>Heart Ventricles - physiopathology</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Lithium - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membrane Potentials - drug effects</subject><subject>Middle Aged</subject><subject>Norepinephrine - pharmacology</subject><subject>Patch-Clamp Techniques</subject><subject>Rabbits</subject><subject>Sodium-Calcium Exchanger - antagonists & inhibitors</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpd0Utr3DAQAGBRWppt2mOvRRTam1ONJFvWsYQ-AoFe2rMZy6Osgi1tJLuQ_Ppq2YVAT0LDN8M8GHsP4gqggy97p42AK2Fta8wLtoNW6ka3yr5kOyGEbYyS8oK9KeW-fjtl2tfsAsBIJaTZsYebFIPjC7k9xlAWnjyfaMZHmjj6lfJEhzRjDk-4hhQLD5H_pbjm4LYa5o7muQZLNWtN8TktfL8tGDnFqSkr3hH3GOYQ7_ieMK_lLXvlcS707vxesj_fv_2-_tnc_vpxc_31tnHa6rUh16q2lzBBj95aOXqtRyOkFqP3rSfXyRH0NNk6MHnTOwc4grIKJHR1UnXJPp_qHnJ62KiswxLKsV2MlLYyHDegTK8r_PgfvE9bjrW3QYLsOtA9VNSckMuplEx-OOSwYH4cQAzHQwynQwynQ1T_4Vx0GxeanvV58xV8OgMsDmefMbpQnp0GUK3q1D8JQJEk</recordid><startdate>20011127</startdate><enddate>20011127</enddate><creator>VERKERK, Arie O</creator><creator>VELDKAMP, Marieke W</creator><creator>BAARTSCHEER, Antonius</creator><creator>SCHUMACHER, Cees A</creator><creator>KLÖPPING, Corinne</creator><creator>VAN GINNEKEN, Antoni C. G</creator><creator>RAVESLOOT, Jan H</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>20011127</creationdate><title>Ionic mechanism of delayed afterdepolarizations in ventricular cells isolated from human end-stage failing hearts</title><author>VERKERK, Arie O ; VELDKAMP, Marieke W ; BAARTSCHEER, Antonius ; SCHUMACHER, Cees A ; KLÖPPING, Corinne ; VAN GINNEKEN, Antoni C. G ; RAVESLOOT, Jan H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c494t-ec535821d18af992bf44b70240bff5fec62b14dd9152ef78cc1ab139312160003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid - pharmacology</topic><topic>Adult</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Calcium - metabolism</topic><topic>Cardiology. Vascular system</topic><topic>Cell Separation</topic><topic>Chloride Channels - antagonists & inhibitors</topic><topic>Disease Models, Animal</topic><topic>Electric Stimulation</topic><topic>Female</topic><topic>Heart</topic><topic>Heart Failure - pathology</topic><topic>Heart Failure - physiopathology</topic><topic>Heart failure, cardiogenic pulmonary edema, cardiac enlargement</topic><topic>Heart Ventricles - drug effects</topic><topic>Heart Ventricles - pathology</topic><topic>Heart Ventricles - physiopathology</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Lithium - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Membrane Potentials - drug effects</topic><topic>Middle Aged</topic><topic>Norepinephrine - pharmacology</topic><topic>Patch-Clamp Techniques</topic><topic>Rabbits</topic><topic>Sodium-Calcium Exchanger - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>VERKERK, Arie O</creatorcontrib><creatorcontrib>VELDKAMP, Marieke W</creatorcontrib><creatorcontrib>BAARTSCHEER, Antonius</creatorcontrib><creatorcontrib>SCHUMACHER, Cees A</creatorcontrib><creatorcontrib>KLÖPPING, Corinne</creatorcontrib><creatorcontrib>VAN GINNEKEN, Antoni C. G</creatorcontrib><creatorcontrib>RAVESLOOT, Jan H</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>VERKERK, Arie O</au><au>VELDKAMP, Marieke W</au><au>BAARTSCHEER, Antonius</au><au>SCHUMACHER, Cees A</au><au>KLÖPPING, Corinne</au><au>VAN GINNEKEN, Antoni C. G</au><au>RAVESLOOT, Jan H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ionic mechanism of delayed afterdepolarizations in ventricular cells isolated from human end-stage failing hearts</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2001-11-27</date><risdate>2001</risdate><volume>104</volume><issue>22</issue><spage>2728</spage><epage>2733</epage><pages>2728-2733</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Animal studies have shown that the Ca(2+)-activated Cl(-) current (I(Cl(Ca))) and the Na(+)/Ca(2+) exchange current (I(Na/Ca)) contribute to the transient inward current (I(ti)). I(ti) is responsible for the proarrhythmic delayed afterdepolarizations (DADs). We investigated the ionic mechanism of I(ti) and DADs in human cardiac cells.
Human ventricular cells were enzymatically isolated from explanted hearts of patients with end-stage heart failure and studied with patch-clamp methodology. I(ti)s were elicited in the presence of 1 micromol/L norepinephrine by trains of repetitive depolarizations from -80 to +50 mV. DADs were induced in the presence of 1 micromol/L norepinephrine at a stimulus frequency of 1 Hz. I(ti) currents were inwardly directed over the voltage range between -110 and + 50 mV. Neither the Cl(-) channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid nor changes in [Cl(-)](i) affected I(ti) or DAD amplitude. This excludes an important role for I(Cl(Ca)). Blockade of Na(+)/Ca(2+) exchange by substitution of all extracellular Na(+) by Li(+), conversely, completely inhibited I(ti). In rabbit, I(Cl(Ca)) density in ventricular cells isolated from control hearts did not differ significantly from that in ventricular cells isolated from failing hearts.
In contrast to many animal species, I(ti) and DADs in human ventricular cells from failing hearts consist only of I(Na/Ca). In rabbits, heart failure per se does not alter I(Cl(Ca)) density, suggesting that I(Cl(Ca)) may also be absent during DADs in nonfailing human ventricular cells.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>11723027</pmid><doi>10.1161/hc4701.099577</doi><tpages>6</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 | 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid - pharmacology Adult Animals Biological and medical sciences Calcium - metabolism Cardiology. Vascular system Cell Separation Chloride Channels - antagonists & inhibitors Disease Models, Animal Electric Stimulation Female Heart Heart Failure - pathology Heart Failure - physiopathology Heart failure, cardiogenic pulmonary edema, cardiac enlargement Heart Ventricles - drug effects Heart Ventricles - pathology Heart Ventricles - physiopathology Humans In Vitro Techniques Lithium - pharmacology Male Medical sciences Membrane Potentials - drug effects Middle Aged Norepinephrine - pharmacology Patch-Clamp Techniques Rabbits Sodium-Calcium Exchanger - antagonists & inhibitors |
| title | Ionic mechanism of delayed afterdepolarizations in ventricular cells isolated from human end-stage failing hearts |
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