Effects of K^+ Channel Modulators on the Relationship Between Action Potential Duration and Ca^<2+> Transients in Single Ventricular Myocytes of the Guinea Pig

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Effects of K<SUP>+</SUP> channel modulators, cromakalim and E4031 [1-[2-(6-methyl-2-pyridyl)-ethyl]-4-(4-methylsulfonylaminobenzoyl) piperidine], on the relationship between the action potential duration (APD) and Ca<SUP>2+</SUP> transients were examined in single myocytes isolated from guinea pig cardiac left ventricle. Application of cromakalim decreased APD at 90% repolarization (APD<SUB>90</SUB>) and Ca<SUP>2+</SUP> transient elicited at 0.5 Hz (IC<SUB>50</SUB>s=0.6 and 3 μM, respectively). Application of 0.3 μM E4031 increased these parameters by 110% and 45%, respectively. Under voltage-clamp, the relation between the duration of depolarization to 0 mV and Ca<SUP>2+</SUP> transients could be described by the sum of two exponential components; the time constants were approximately 5 and 280 msec, respectively. The first component was abolished by 10 μM ryanodine, suggesting the involvement of Ca<SUP>2+</SUP>-induced Ca<SUP>2+</SUP> release (CICR). Neither cromakalim nor E4031 directly affected Ca<SUP>2+</SUP> current and Ca<SUP>2+</SUP> transients under voltage clamp. When APD was changed by K<SUP>+</SUP> channel modulators, the relation between APD<SUB>90</SUB> and Ca<SUP>2+</SUP>-transients was almost similar to that obtained by changing the depolarization duration under voltage-clamp. CICR was changed significantly only when APD<SUB>90</SUB> was markedly shortened by cromakalim. The extensively prolonged AP and Ca<SUP>2+</SUP> transient in the presence of E4031 were reduced by an addition of cromakalim. It is concluded that these two K<SUP>+</SUP> channel modulators can significantly alter the AP-induced Ca<SUP>2+</SUP> transient mainly by changing APD, which regulates both Ca<SUP>2+</SUP> influx and extrusion.

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  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 80(3), 243-253, 1999-07

    公益社団法人 日本薬理学会

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各種コード

  • NII論文ID(NAID)
    10008195375
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    JPN
  • 資料種別
    ART
  • ISSN
    00215198
  • NDL 記事登録ID
    4806312
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  NDL  J-STAGE 
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