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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1992-9-17
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pubmed:abstractText |
alpha 1-Adrenoceptor activation can enhance myocardial contractility, and two possible inotropic mechanisms are an increase in myofilament Ca2+ sensitivity and action potential prolongation, which can increase net Ca2+ entry into cells. In adult rat ventricular myocytes (bath Ca2+, 1 mM; stimulated at 0.2-0.5 Hz), the drug 4-aminopyridine and the whole-cell voltage clamp have been used to control Ca2+ entry and differentiate between the two mechanisms. At 22-23 degrees C the specific alpha 1-adrenoceptor agonist methoxamine (100 microM) prolonged action potential duration at 50% repolarization from 55 +/- 2 to 81 +/- 5 msec, delayed time to peak contraction, and increased shortening amplitude from 5.3 +/- 0.6 to 7.8 +/- 1 microns (n = 18). Reduction of the transient outward current and other K+ currents by methoxamine was the major cause of action potential prolongation in rat myocytes with little change in the L-type calcium current. Block of the transient outward current with 2 mM 4-aminopyridine prolonged action potential duration from 52 +/- 6 to 98 +/- 12 msec and increased unloaded cell shortening from 2.9 +/- 0.4 to 6.6 +/- 0.6 microns (n = 4). Subsequently, methoxamine no longer increased cell shortening, although significant potentiation of twitch amplitude was still seen after a brief rest interval. In voltage-clamp experiments, with 70-500-msec pulses, although membrane currents were reduced, methoxamine had no positive inotropic effect and reduced cell shortening from 5.3 +/- 0.7 to 4.97 +/- 0.8 microns at pulse potentials positive to -40 mV. Similar alpha 1-adrenoceptor responses were observed at 35 degrees C during action potential and voltage-clamp experiments, which could be blocked by 10 microM prazosin. In myocytes loaded with the Ca2+ indicator indo-1, alpha 1-adrenoceptor stimulation or 4-aminopyridine both increased cell contraction and intracellular Ca2+ transients by similar amounts. As in unloaded cells, prior exposure to 4-aminopyridine prevented any inotropic effect of methoxamine without changing the systolic intracellular Ca2+ transient. The results indicated that under our experimental conditions positive inotropy in rat cardiomyocytes on exposure to alpha 1-adrenoceptor agonists was strongly correlated with the action potential prolongation that accompanied K+ current reduction. In addition, modulation of K+ channels could occur independent of changes in contractility and/or [Ca2+]i.
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pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-Aminopyridine,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Methoxamine,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, alpha,
http://linkedlifedata.com/resource/pubmed/chemical/indo-1
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0009-7330
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
71
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
673-88
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:1323437-4-Aminopyridine,
pubmed-meshheading:1323437-Actin Cytoskeleton,
pubmed-meshheading:1323437-Action Potentials,
pubmed-meshheading:1323437-Animals,
pubmed-meshheading:1323437-Calcium,
pubmed-meshheading:1323437-Heart,
pubmed-meshheading:1323437-Indoles,
pubmed-meshheading:1323437-Methoxamine,
pubmed-meshheading:1323437-Myocardial Contraction,
pubmed-meshheading:1323437-Myocardium,
pubmed-meshheading:1323437-Potassium Channels,
pubmed-meshheading:1323437-Rats,
pubmed-meshheading:1323437-Receptors, Adrenergic, alpha
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pubmed:year |
1992
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pubmed:articleTitle |
Mechanisms for the positive inotropic effect of alpha 1-adrenoceptor stimulation in rat cardiac myocytes.
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pubmed:affiliation |
Department of Physiology, Queen's University, Kingston, Canada.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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