L-type Ca2+ current in guinea pig ventricular myocytes treated with modulators of tyrosine phosphorylation.

L-type Ca2+ current in guinea pig ventricular myocytes treated with modulators of tyrosine phosphorylation.
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用酪氨酸磷酸化调节剂处理的豚鼠心室肌​​细胞中的 L 型 Ca2 电流。

DOI:
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发表时间:
1999
期刊:
American Journal of Physiology. Heart and Circulatory Physiology
影响因子:
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通讯作者:
T. Mcdonald
T. Mcdonald
中科院分区:
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文献类型:
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作者:
T. Ogura;L. Shuba;T. Mcdonald

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用酪氨酸激酶(TK)抑制剂[染料木素(Gst), tyrphostin A23 (T23)和tyrphostin A25 (T25)]和无活性类似物[大豆苷元,genistin和tyrphostin A1 (T1)]处理豚鼠心室肌细胞,以测量对L型Ca2+电流(I Ca,L)的影响。Gst抑制I - Ca,L(IC50 = 47 μM),但不影响其时间进程或改变I - Ca,L-电压关系。在最高异黄酮浓度(200 μM)下,I Ca,L分别被66±7% (Gst)、22±2%(大豆苷元)和1±3%(龙胆素)抑制。活性tyrphostiins对I、Ca、L的抑制作用显著大于T1的抑制作用;在200 μM时,抑制率分别为72±6% (T23)、71±6% (T25)和27±6% (T1)。磷酸酪氨酸磷酸酶抑制剂正钒酸盐(1 mM)对基础I Ca,L有较小的刺激作用(6±2%),阻断了TK抑制剂对I Ca,L的抑制作用。这些数据表明tk -磷酸酪氨酸磷酸酶系统在心脏Ca2+通道调节中的作用。
Guinea pig ventricular myocytes in whole cell configuration were treated with tyrosine kinase (TK) inhibitors [genistein (Gst), tyrphostin A23 (T23), and tyrphostin A25 (T25)] and with inactive analogs [daidzein, genistin, and tyrphostin A1 (T1)] to measure effects on L-type Ca2+ current ( I Ca,L). Gst inhibited I Ca,L(IC50 = 47 μM) without affecting its time course or shifting the I Ca,L-voltage relationship. At the highest concentration of isoflavone tested (200 μM), I Ca,L was inhibited by 66 ± 7% (Gst), 22 ± 2% (daidzein), and 1 ± 3% (genistin). Inhibition of I Ca,L by the active tyrphostins was significantly larger than inhibition by T1; at 200 μM the inhibitions were 72 ± 6% (T23), 71 ± 6% (T25), and 27 ± 6% (T1). The phosphotyrosine phosphatase inhibitor orthovanadate (1 mM) had a small stimulatory effect (6 ± 2%) on basal I Ca,L and blocked the inhibition of I Ca,L by TK inhibitors. The data suggest a role for the TK-phosphotyrosine phosphatase system in the regulation of cardiac Ca2+ channels.
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