Na(+)/Ca(2+) exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart
The Na(+)/Ca(2+) exchanger (NCX) may play a key role in myocardial contractility. The operation of the NCX is affected by the action potential (AP) configuration and the intracellular Na(+) concentration. This study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 microM SEA0400 o...
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| Veröffentlicht in: | British journal of pharmacology 2008-05, Vol.154 (1), p.93-104 |
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| creator | Farkas, A S Acsai, K Nagy, N Tóth, A Fülöp, F Seprényi, G Birinyi, P Nánási, P P Forster, T Csanády, M Papp, J G Varró, A Farkas, A |
| description | The Na(+)/Ca(2+) exchanger (NCX) may play a key role in myocardial contractility. The operation of the NCX is affected by the action potential (AP) configuration and the intracellular Na(+) concentration. This study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 microM SEA0400 on the myocardial contractility in the setting of different AP configurations and different intracellular Na(+) concentrations in rabbit and rat hearts.
The concentration-dependent effects of SEA0400 on I(Na/Ca) were studied in rat and rabbit ventricular cardiomyocytes using a patch clamp technique. Starling curves were constructed for isolated, Langendorff-perfused rat and rabbit hearts. The cardiac sarcolemmal NCX protein densities of both species were compared by immunohistochemistry.
SEA0400 inhibited I(Na/Ca) with similar efficacy in the two species; there was no difference between the inhibitions of the forward or reverse mode of the NCX in either species. SEA0400 increased the systolic and the developed pressure in the rat heart in a concentration-dependent manner, for example, 1.0 microM SEA0400 increased the maximum systolic pressures by 12% relative to the control, whereas it failed to alter the contractility in the rabbit heart. No interspecies difference was found in the cardiac sarcolemmal NCX protein densities.
NCX inhibition exerted a positive inotropic effect in the rat heart, but it did not influence the contractility of the rabbit heart. This implies that the AP configuration and the intracellular Na(+) concentration may play an important role in the contractility response to NCX inhibition. |
| doi_str_mv | 10.1038/bjp.2008.83 |
| format | Article |
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The concentration-dependent effects of SEA0400 on I(Na/Ca) were studied in rat and rabbit ventricular cardiomyocytes using a patch clamp technique. Starling curves were constructed for isolated, Langendorff-perfused rat and rabbit hearts. The cardiac sarcolemmal NCX protein densities of both species were compared by immunohistochemistry.
SEA0400 inhibited I(Na/Ca) with similar efficacy in the two species; there was no difference between the inhibitions of the forward or reverse mode of the NCX in either species. SEA0400 increased the systolic and the developed pressure in the rat heart in a concentration-dependent manner, for example, 1.0 microM SEA0400 increased the maximum systolic pressures by 12% relative to the control, whereas it failed to alter the contractility in the rabbit heart. No interspecies difference was found in the cardiac sarcolemmal NCX protein densities.
NCX inhibition exerted a positive inotropic effect in the rat heart, but it did not influence the contractility of the rabbit heart. This implies that the AP configuration and the intracellular Na(+) concentration may play an important role in the contractility response to NCX inhibition.</description><identifier>ISSN: 0007-1188</identifier><identifier>DOI: 10.1038/bjp.2008.83</identifier><identifier>PMID: 18332852</identifier><language>eng</language><publisher>England</publisher><subject>Action Potentials - drug effects ; Aniline Compounds - pharmacology ; Animals ; Blood Pressure - drug effects ; Cardiotonic Agents - pharmacology ; Coronary Circulation - drug effects ; Electrocardiography - drug effects ; Heart - drug effects ; Heart Rate - drug effects ; Immunohistochemistry ; Microscopy, Confocal ; Myocardial Contraction - drug effects ; Myocytes, Cardiac - drug effects ; Patch-Clamp Techniques ; Phenyl Ethers - pharmacology ; Rabbits ; Rats ; Sodium-Calcium Exchanger - antagonists & inhibitors ; Species Specificity</subject><ispartof>British journal of pharmacology, 2008-05, Vol.154 (1), p.93-104</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18332852$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Farkas, A S</creatorcontrib><creatorcontrib>Acsai, K</creatorcontrib><creatorcontrib>Nagy, N</creatorcontrib><creatorcontrib>Tóth, A</creatorcontrib><creatorcontrib>Fülöp, F</creatorcontrib><creatorcontrib>Seprényi, G</creatorcontrib><creatorcontrib>Birinyi, P</creatorcontrib><creatorcontrib>Nánási, P P</creatorcontrib><creatorcontrib>Forster, T</creatorcontrib><creatorcontrib>Csanády, M</creatorcontrib><creatorcontrib>Papp, J G</creatorcontrib><creatorcontrib>Varró, A</creatorcontrib><creatorcontrib>Farkas, A</creatorcontrib><title>Na(+)/Ca(2+) exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>The Na(+)/Ca(2+) exchanger (NCX) may play a key role in myocardial contractility. The operation of the NCX is affected by the action potential (AP) configuration and the intracellular Na(+) concentration. This study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 microM SEA0400 on the myocardial contractility in the setting of different AP configurations and different intracellular Na(+) concentrations in rabbit and rat hearts.
The concentration-dependent effects of SEA0400 on I(Na/Ca) were studied in rat and rabbit ventricular cardiomyocytes using a patch clamp technique. Starling curves were constructed for isolated, Langendorff-perfused rat and rabbit hearts. The cardiac sarcolemmal NCX protein densities of both species were compared by immunohistochemistry.
SEA0400 inhibited I(Na/Ca) with similar efficacy in the two species; there was no difference between the inhibitions of the forward or reverse mode of the NCX in either species. SEA0400 increased the systolic and the developed pressure in the rat heart in a concentration-dependent manner, for example, 1.0 microM SEA0400 increased the maximum systolic pressures by 12% relative to the control, whereas it failed to alter the contractility in the rabbit heart. No interspecies difference was found in the cardiac sarcolemmal NCX protein densities.
NCX inhibition exerted a positive inotropic effect in the rat heart, but it did not influence the contractility of the rabbit heart. This implies that the AP configuration and the intracellular Na(+) concentration may play an important role in the contractility response to NCX inhibition.</description><subject>Action Potentials - drug effects</subject><subject>Aniline Compounds - pharmacology</subject><subject>Animals</subject><subject>Blood Pressure - drug effects</subject><subject>Cardiotonic Agents - pharmacology</subject><subject>Coronary Circulation - drug effects</subject><subject>Electrocardiography - drug effects</subject><subject>Heart - drug effects</subject><subject>Heart Rate - drug effects</subject><subject>Immunohistochemistry</subject><subject>Microscopy, Confocal</subject><subject>Myocardial Contraction - drug effects</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Patch-Clamp Techniques</subject><subject>Phenyl Ethers - pharmacology</subject><subject>Rabbits</subject><subject>Rats</subject><subject>Sodium-Calcium Exchanger - antagonists & inhibitors</subject><subject>Species Specificity</subject><issn>0007-1188</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kD1PwzAQhj2AaClM7MgToipp7dhOnRFVfEkVLDBHtnMhrtI42A6iv4M_TKBlOul5n_dOOoQuKJlTwuRCb7p5SoicS3aExoSQZUKplCN0GsKGEMqXS3GCRlQylkqRjtH3s7qeTRcrdZ3Ophi-TK3ad_DYtrXVNlrXDhB8DFjhzoWBfMIQuuhdZw2GqgITB4BjDdiriGtQPt5g3UdcKdsEHN0QV00PrYE_y7g2emWibWzcYVcdqno4t2-foeNKNQHOD3OC3u7vXlePyfrl4Wl1u046mvKYcOCl0pnImKaMCFpmUglp0pwrKQUrearzAWuhSKZkJokY7DKHTApuSJayCbra7-28--ghxGJrg4GmUS24PhRZTjkn4le8PIi93kJZdN5uld8V_29kPwYpchY</recordid><startdate>200805</startdate><enddate>200805</enddate><creator>Farkas, A S</creator><creator>Acsai, K</creator><creator>Nagy, N</creator><creator>Tóth, A</creator><creator>Fülöp, F</creator><creator>Seprényi, G</creator><creator>Birinyi, P</creator><creator>Nánási, P P</creator><creator>Forster, T</creator><creator>Csanády, M</creator><creator>Papp, J G</creator><creator>Varró, A</creator><creator>Farkas, A</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>200805</creationdate><title>Na(+)/Ca(2+) exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart</title><author>Farkas, A S ; Acsai, K ; Nagy, N ; Tóth, A ; Fülöp, F ; Seprényi, G ; Birinyi, P ; Nánási, P P ; Forster, T ; Csanády, M ; Papp, J G ; Varró, A ; Farkas, A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p124t-4e4dab6563b13051d68a58c294a8853d42b9051b5a06a86805ab6d9e6854c0623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Action Potentials - drug effects</topic><topic>Aniline Compounds - pharmacology</topic><topic>Animals</topic><topic>Blood Pressure - drug effects</topic><topic>Cardiotonic Agents - pharmacology</topic><topic>Coronary Circulation - drug effects</topic><topic>Electrocardiography - drug effects</topic><topic>Heart - drug effects</topic><topic>Heart Rate - drug effects</topic><topic>Immunohistochemistry</topic><topic>Microscopy, Confocal</topic><topic>Myocardial Contraction - drug effects</topic><topic>Myocytes, Cardiac - drug effects</topic><topic>Patch-Clamp Techniques</topic><topic>Phenyl Ethers - pharmacology</topic><topic>Rabbits</topic><topic>Rats</topic><topic>Sodium-Calcium Exchanger - antagonists & inhibitors</topic><topic>Species Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Farkas, A S</creatorcontrib><creatorcontrib>Acsai, K</creatorcontrib><creatorcontrib>Nagy, N</creatorcontrib><creatorcontrib>Tóth, A</creatorcontrib><creatorcontrib>Fülöp, F</creatorcontrib><creatorcontrib>Seprényi, G</creatorcontrib><creatorcontrib>Birinyi, P</creatorcontrib><creatorcontrib>Nánási, P P</creatorcontrib><creatorcontrib>Forster, T</creatorcontrib><creatorcontrib>Csanády, M</creatorcontrib><creatorcontrib>Papp, J G</creatorcontrib><creatorcontrib>Varró, A</creatorcontrib><creatorcontrib>Farkas, A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Farkas, A S</au><au>Acsai, K</au><au>Nagy, N</au><au>Tóth, A</au><au>Fülöp, F</au><au>Seprényi, G</au><au>Birinyi, P</au><au>Nánási, P P</au><au>Forster, T</au><au>Csanády, M</au><au>Papp, J G</au><au>Varró, A</au><au>Farkas, A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Na(+)/Ca(2+) exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2008-05</date><risdate>2008</risdate><volume>154</volume><issue>1</issue><spage>93</spage><epage>104</epage><pages>93-104</pages><issn>0007-1188</issn><abstract>The Na(+)/Ca(2+) exchanger (NCX) may play a key role in myocardial contractility. The operation of the NCX is affected by the action potential (AP) configuration and the intracellular Na(+) concentration. This study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 microM SEA0400 on the myocardial contractility in the setting of different AP configurations and different intracellular Na(+) concentrations in rabbit and rat hearts.
The concentration-dependent effects of SEA0400 on I(Na/Ca) were studied in rat and rabbit ventricular cardiomyocytes using a patch clamp technique. Starling curves were constructed for isolated, Langendorff-perfused rat and rabbit hearts. The cardiac sarcolemmal NCX protein densities of both species were compared by immunohistochemistry.
SEA0400 inhibited I(Na/Ca) with similar efficacy in the two species; there was no difference between the inhibitions of the forward or reverse mode of the NCX in either species. SEA0400 increased the systolic and the developed pressure in the rat heart in a concentration-dependent manner, for example, 1.0 microM SEA0400 increased the maximum systolic pressures by 12% relative to the control, whereas it failed to alter the contractility in the rabbit heart. No interspecies difference was found in the cardiac sarcolemmal NCX protein densities.
NCX inhibition exerted a positive inotropic effect in the rat heart, but it did not influence the contractility of the rabbit heart. This implies that the AP configuration and the intracellular Na(+) concentration may play an important role in the contractility response to NCX inhibition.</abstract><cop>England</cop><pmid>18332852</pmid><doi>10.1038/bjp.2008.83</doi><tpages>12</tpages></addata></record> |
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| subjects | Action Potentials - drug effects Aniline Compounds - pharmacology Animals Blood Pressure - drug effects Cardiotonic Agents - pharmacology Coronary Circulation - drug effects Electrocardiography - drug effects Heart - drug effects Heart Rate - drug effects Immunohistochemistry Microscopy, Confocal Myocardial Contraction - drug effects Myocytes, Cardiac - drug effects Patch-Clamp Techniques Phenyl Ethers - pharmacology Rabbits Rats Sodium-Calcium Exchanger - antagonists & inhibitors Species Specificity |
| title | Na(+)/Ca(2+) exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart |
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