EFFECTS OF NEUROENDOCRINAL FACTORS ON CARDIAC SODIUM-CALCIUM EXCHANGER

神经内分泌因素对心脏钠钙交换的影响

• 批准号: 11670096
• 负责人: KIMURA Junko
• 金额: $ 2.3万
• 依托单位: Fukushima Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670096/
• 关键词: SODIUM-CALCIUM EXCHANGE CURRENT; WHOLECELPATCH CLAMP; GUINEA PIG; PHOSPHORYLATION; DEPHOSPHORYLATION; CALCIUM; SODIUM; ANTIARRHYTHMIC DRUGS; sodium-calcium exchange; cardiac myocytes; whole cell clamp; guinea pig; transporter; inhibitor; hea

1) As neuroendocrine factors, we tested effects on Na^+/Ca^<2+> exchange current (I_<NCX>) of angiotensin II, endothelin, epinephrine and phenylephrine with the whole cell voltage clamp method using single guinea-pig cardiac ventricular cells. However, none of them exerted effects on Na-Ca exchange current (I_<NCX>)2) Butanedione monoxime (BDM) is called a chemical phosphatase. We found that BDM inhibited I_<NCX>. We tested whether the effect of BDM was due to dephosphorylation of NCX. Activation of A-kinase and C kinase did not affect NCX. NCX1 mutants with possible phosphorylation site serines replaced by alanines were also inhibited by BDM. Therefore we concluded that phosphorylation and dephosphorylation mechanisms are not involved in the inhibitory effects of BDM on NCX.3) Interaction of NCX with Na-H exchange was investigated by measuring the reversal potential (E_<NCX>) of I_<NCX> before and after acidification to pH4.9 from pH7.4. E_<NCX> shifted in the negative direction by acidification. The negative shift was inhibited by inhibitors of Na-H exchanger and enhanced by Na-H exchange accelerator. Addition of Na-H exchange inhibitor only during the recovery from acidification also prevented shift in E_<NCX>, indicating that Na-H exchange was inhibited by acid. These results suggest that Na-H exchange and Na-Ca exchange are closely linked to each other. Increase in Na_I increased during recovery from acidification was calculated to be about 3 mM.

1）作为神经内分泌因子，我们测试了血管紧张素II，内皮素，肾上腺素和苯肾上腺素的Na^+/ca^<2+>交换电流（I_ <ncx>），并使用单豚鼠钳位方法心室细胞。但是，它们都没有对Na-Ca交换电流（I_ <ncx>）2）施加影响。我们发现BDM抑制了I_ <ncx>。我们测试了BDM的作用是否是由于NCX的去磷酸化引起的。 A-激酶和C激酶的激活不会影响NCX。 BDM也抑制了由磷酸化位点丝氨酸取代的NCX1突变体。因此，我们得出的结论是，通过测量I_ <ncx>的逆转电位（E_ <ncx>），研究了NCX与Na-H交换的NCX相互作用的磷酸化和去磷酸化机制不参与BDM对NCX的抑制作用。从PH7.4酸化为PH4.9后。 E_ <NCX>通过酸化向负方向移动。 Na-H交换器的抑制剂抑制了负变化，并通过Na-H交换加速器增强。仅在从酸化中恢复过程中，添加Na-H交换抑制剂也阻止了E_ <ncx>的转移，这表明Na-H交换被酸抑制。这些结果表明，NA-H交换和NA-CA交换彼此紧密相关。从酸化过程中，Na_i的增加计算为约3 mm。

项目成果

Katoh Y,Hashimoto S, Kimura J,Watanabe T.: "Inhibitory action of troglitazone, an insulin-sensitizing agent, on the calcium current in cardiac ventricular cells of guinea pig."Japanese Journal of Pharmacology. 82. 102-109 (2000)

Katoh Y，Hashimoto S，Kimura J，Watanabe T.：“胰岛素增敏剂曲格列酮对豚鼠心室细胞钙电流的抑制作用。”日本药理学杂志。

Kimura J.: "Sodium-calcium exchanger heart cells"11th International Conference of Women Engineers and scieutists. 969-974 (1999)

Kimura J.：“钠钙交换心脏细胞”第11届国际女工程师和科学家会议。

WATANABE Yasuhide, KIMURA Junko: "Blocking effect of bepridil on Na^+/Ca^<2+> exchange current in guinea pig cardiac ventricular myocytes"Jpn. J. Pharmacol. 85. 370-375 (2001)

WATANABE Yasuhide、KIMURA Junko：“苯普地尔对豚鼠心室肌​​细胞 Na^ /Ca^2 > 交换电流的阻断作用”Jpn。

Kimura J.: "Cardiac Na^+/Ca^<2+> exchanger : Pathophysiology and pharmacology.In : Heart Physiology and Pathology"Sperelakis N, Kurachi Y, Terzic A, Cohen MV. 419-425 (2000)

Kimura J.：“心脏Na ^ /Ca ^ 2 >交换器：病理生理学和药理学。在：心脏生理学和病理学”Sperelakis N，Kurachi Y，Terzic A，Cohen MV。

Katoh Y,Hashimoto S,Kimura J,Watanabe T.: "Inhibitory action of Troglitazone,an insulin-sencitizing agent,on the calcium current in cardiuc ventricular cells of guineapig"Jpn.J.Pharmacol.. 82. 102-109 (2000)

加藤 Y、桥本 S、木村 J、渡边 T.：“胰岛素敏化剂曲格列酮对豚鼠心室细胞钙电流的抑制作用”Jpn.J.Pharmacol.. 82. 102-109 (2000)