Regulation of L‐type calcium channels by protein tyrosine kinase and protein kinase C in cultured rat and human retinal pigment epithelial cells 1

Regulation of L‐type calcium channels by protein tyrosine kinase and protein kinase C in cultured rat and human retinal pigment epithelial cells 1
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蛋白酪氨酸激酶和蛋白激酶 C 对培养的大鼠和人视网膜色素上皮细胞中 L 型钙通道的调节 1

DOI:
10.1096/fasebj.11.11.9285484
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发表时间:
1997
期刊:
The FASEB Journal
影响因子:
--
通讯作者:
Michael Wbederholt
Michael Wbederholt
中科院分区:
--
文献类型:
--
作者:
O. Strauß;S. Mergler;Michael Wbederholt

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The effect of protein tyrosine kinases (PTKs) on L‐type calcium channel currents was studied in cultured rat and human retinal pigment epithelial cells. Barium currents through L‐type channels were measured in the perforated patch‐clamp technique and identified by using the L‐type calcium channel opener Bay K8644 (10−6 M). Application of the PTK blockers genistein (5 × 10−6 M) or lavendustin A (5×10−6 M) led to a decrease of L‐type currents. The inactive genistein analog daidzein (10−5 M) showed no effect on calcium channels. Intracellular application of pp60c‐src (30 U/ml) via the patch‐pipette during the conventional whole‐cell configuration led to an increase of L‐type currents. The protein kinase A and protein kinase G blocker H9 (10−6 M) showed no effect on L‐type currents; genistein reduced the current in the presence of H9. The protein kinase C (PKC) blocker chelerythrine (10−5 M) reduced the L‐type current; additional inhibition of PTK by lavendustin showed an additional reduction of currents. Intracellular application of myristoylated PKC substrate (5×10−5 M) for PKC inhibition led to a fast rundown of L‐type current amplitudes. Intracellularly applied myristoylated PKC substrate (10−4 M) together with pp60c‐src showed no effect on L‐type current. Up‐regulation of PKC by 10−6 M phorbol‐12‐myristate‐13‐acetate (PMA) had no effect on the L‐type current amplitude. However, genistein in cells pretreated with PMA led to an increase of the L‐type currents. Intracellular application of pp60c‐src in PMA‐treated cells led to a reduction of L‐type currents. We conclude that in the resting cell, PTK and PKC regulate L‐type calcium channels in an additive manner. L‐type channels appeared as a site of integration of PTK activation and of PKC‐dependent pathways. The activity of PKC determines whether PTK decreases or increases L‐type channel activity.—Strauss, O., Mergler, S., Wiederholt, M. Regulation of L‐type calcium channels by protein tyrosine kinase and protein kinase C in cultured rat and human retinal pigment epithelial cells. FASEB J. 11, 859–867 (1997)
DOI: 10.1021/bi00095a020
发表时间: 1993-11
期刊: Biochemistry
影响因子: 2.9
作者:
N. Ward;C. O'brian
通讯作者: N. Ward;C. O'brian
新鲜和培养的大鼠视网膜色素上皮细胞中电压控制的钙通道。
DOI: --
发表时间: 1993
影响因子: 4.4
作者:
Ueda,Y;Steinberg,RH
通讯作者: Steinberg,RH