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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1995-5-11
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pubmed:abstractText |
The bradycardic mechanism of ZD 7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)pyrimidinium++ + chloride) was investigated in sheep cardiac Purkinje fibres. The pacemaker i(f)-current measured with the two-microelectrode voltage-clamp technique, as well as the diastolic depolarization rate and the frequency of spontaneously active fibres were evaluated. ZD 7288 did inhibit i(f)-current. The i(f)-amplitude recorded with a 0.8s-lasting test pulse from about -50 mV to -100 mV was reduced to 50% of control at 0.85 mumol/l and to 5% of control at 10 mumol/l. The threshold potential of i(f)-activation was unaffected at a concentration of 1 mumol/l ZD 7288. The time constant of i(f)-activation at different test potentials was not changed by 1 mumol/l ZD 7288. The drug was equally effective during i(f)-activation with a 0.5 s-lasting test pulse applied at 0.05 Hz or 0.5 Hz. During long lasting (5 s) hyperpolarizing test pulses (-120 mV) the inhibition of i(f)-current was removed. In constantly stimulated Purkinje fibres (0.5 Hz) the slope of the early diastolic depolarization was decreased by ZD 7288. The half-maximal effect occurred at 0.92 mumol/l. There was strong correlation over the concentration range of 0.01 to 10 mumol/l ZD 7288 between the decrease of the slope of early diastolic depolarization and inhibition of i(f)-amplitude recorded with 0.8s-lasting test pulses to -100 mV. The correlation coefficient was r = 0.97. These results will explain the decrease in frequency of spontaneously active (about 0.6 Hz) Purkinje fibres.(ABSTRACT TRUNCATED AT 250 WORDS)
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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/Cardiotonic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Cesium,
http://linkedlifedata.com/resource/pubmed/chemical/ICI D2788,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0028-1298
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
350
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
677-84
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pubmed:dateRevised |
2003-11-14
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pubmed:meshHeading |
pubmed-meshheading:7708125-Action Potentials,
pubmed-meshheading:7708125-Animals,
pubmed-meshheading:7708125-Cardiotonic Agents,
pubmed-meshheading:7708125-Cell Membrane,
pubmed-meshheading:7708125-Cesium,
pubmed-meshheading:7708125-Heart Conduction System,
pubmed-meshheading:7708125-Potassium Compounds,
pubmed-meshheading:7708125-Purkinje Fibers,
pubmed-meshheading:7708125-Pyrimidines,
pubmed-meshheading:7708125-Sheep
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pubmed:year |
1994
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pubmed:articleTitle |
Effects of the bradycardic agent ZD 7288 on membrane voltage and pacemaker current in sheep cardiac Purkinje fibres.
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pubmed:affiliation |
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Germany.
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pubmed:publicationType |
Journal Article
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