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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1991-2-7
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pubmed:abstractText |
The mechanism by which isoproterenol (ISO) prevents the prolongation of action potential duration (APD) and refractory period (RP) by the class III antiarrhythmic agent E-4031 was studied. E-4031 (1 microM) increased RP by 50% with no effect on contractile force in papillary muscles isolated from guinea pig heart. ISO (1 microM) increased force of contraction more than fivefold and decreased RP by 25%. The prolongation of RP by E-4031 was prevented by pretreatment of muscles with ISO. The prolongation of APD in isolated guinea pig ventricular myocytes by 5 microM E-4031 also was antagonized by prior exposure of the cells to 1 microM ISO. Instantaneous currents and delayed rectifier K+ currents, IK, were measured in isolated myocytes using the suction microelectrode voltage-clamp technique. Currents were measured in response to 225-msec depolarizing pulses from a holding potential of -40 mV. Previous studies have demonstrated that IK in these cells results from activation of two distinct outward K+ currents, IKs and IKr (specifically blocked by E-4031). ISO doubled the magnitude of IKs without significant effect on IKr. The instantaneous current, putatively identified as a Cl- current, also was doubled by ISO but was unaffected by E-4031. The augmented conductance of IKs and instantaneous current by ISO results in a decrease in RP. The small effect of E-4031 on APD and RP in the presence of ISO results from the smaller contribution of IKr relative to the augmented repolarizing currents.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Arrhythmia Agents,
http://linkedlifedata.com/resource/pubmed/chemical/E 4031,
http://linkedlifedata.com/resource/pubmed/chemical/Isoproterenol,
http://linkedlifedata.com/resource/pubmed/chemical/Piperidines,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0009-7330
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
68
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
77-84
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:1984874-Action Potentials,
pubmed-meshheading:1984874-Animals,
pubmed-meshheading:1984874-Anti-Arrhythmia Agents,
pubmed-meshheading:1984874-Cell Separation,
pubmed-meshheading:1984874-Electric Conductivity,
pubmed-meshheading:1984874-Guinea Pigs,
pubmed-meshheading:1984874-Heart,
pubmed-meshheading:1984874-Isoproterenol,
pubmed-meshheading:1984874-Myocardium,
pubmed-meshheading:1984874-Papillary Muscles,
pubmed-meshheading:1984874-Piperidines,
pubmed-meshheading:1984874-Pyridines,
pubmed-meshheading:1984874-Refractory Period, Electrophysiological
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pubmed:year |
1991
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pubmed:articleTitle |
Isoproterenol antagonizes prolongation of refractory period by the class III antiarrhythmic agent E-4031 in guinea pig myocytes. Mechanism of action.
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pubmed:affiliation |
Merck Sharp & Dohme Research Laboratories, Department of Pharmacology, West Point, Pa 19486.
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pubmed:publicationType |
Journal Article,
In Vitro
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