Specific inhibition of stretch-induced increase in L-type calcium channel currents by herbimycin A in canine basilar arterial myocytes
Specific inhibition of stretch-induced increase in L-type calcium channel currents by herbimycin A in canine basilar arterial myocytes
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DOI：
10.1038/sj.bjp.0703360
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发表时间：
2000-06-01
影响因子：
7.3
通讯作者：
Nakayama, K
中科院分区：
文献类型：
--
作者：
Kimura, M;Obara, K;Nakayama, K
1采用全细胞膜片钳技术研究了蛋白酪氨酸激酶（PTK）和蛋白酪氨酸磷酸酶（PTP）抑制剂对低渗溶液增加的犬基底动脉心肌细胞L-型钙通道电压激活钡电流（I-Ba）的影响。型钙通道激动剂Bay K 8643（100 nM）和L型钙通道阻断剂尼卡地平（1 μ M）。3低渗灌流液诱导细胞肿胀并作为牵张刺激，其可逆地增加+10 mV处的峰值I-Ba幅度。在低渗条件下，尼卡地平（1 μ M）也降低了I-Ba。4 PTK抑制剂，如除莠霉素A（30 nM），染料木素（10 μ M），和laviustin A（10 μ M）降低了I-Ba增强的低渗溶液。在等渗条件下，染料木黄酮还以浓度依赖性方式降低I-Ba。无活性染料木黄酮类似物大豆苷元（10 μ M）在等渗或低渗条件下对I-Ba没有影响。相比之下，除莠霉素A在等渗条件下不降低I-Ba。原钒酸钠（10 μ M），一种PTP抑制剂，在两种条件下都增加了I-Ba。5目前的结果表明，低渗溶液引起的细胞肿胀增加了犬基底动脉中的L-型钙通道电流，并且除草霉素敏感的PTK活性主要参与了钙通道电流的增强。
1 The effects of protein-tyrosine kinase (PTK) and protein-tyrosine phosphatase (PTP) inhibitors on voltage-activated barium currents (I-Ba) through L-type calcium channels increased by hypotonic solution were investigated in canine basilar arterial myocytes by the whole-cell patch-clamp technique.2 I-Ba was elicited by depolarizing step from a holding potential of - 80 to + 10 mV and identified by using an L-type calcium channel agonist, Bay K 8643 (100 nM), and an L-type calcium channel blocker, nicardipine (1 mu M).3 Hypotonic superfusate induced cell swelling and acted as a stretch stimulus, which reversibly increased peak I-Ba amplitude at +10 mV. I-Ba was also decreased by nicardipine (1 mu M) under the hypotonic condition.4 PTK inhibitors such as herbimycin A (30 nM), genistein (10 mu M), and lavendustin A (10 mu M) decreased I-Ba enhanced by hypotonic solution. Genistein also decreased I-Ba in a concentration-dependent manner under the isotonic condition. The inactive genistein analogue daidzein (10 mu M) had no effect on I-Ba under either the isotonic or hypotonic condition. By contrast, herbimycin A did not decrease I-Ba under the isotonic condition. Sodium orthovanadate (10 mu M), a PTP inhibitor, increased I-Ba under both conditions.5 The present results suggest that cell swelling by hypotonic solution increases the L-type calcium channel currents in canine basilar artery and that herbimycin-sensitive PTK activity is primarily involved in the enhancement of calcium channel currents.