Involvement of protein kinase C and protein kinase A in the enhancement of L-type calcium current by GABAB receptor activation in neonatal hippocampus.
Involvement of protein kinase C and protein kinase A in the enhancement of L-type calcium current by GABAB receptor activation in neonatal hippocampus.
复制标题
DOI：
10.1016/j.neuroscience.2011.01.054
复制
发表时间：
2011-04-14
期刊：
影响因子：
3.3
通讯作者：
Mynlieff, M.
中科院分区：
文献类型：
--
作者：
Bray, J. G.;Mynlieff, M.
在新生早期，GABAB受体的激活减弱了大鼠海马神经元通过N型钙通道的钙电流，同时增强了通过L型钙通道的钙电流。N型钙电流的衰减以前已被证明是通过Gi/o G蛋白的βγ亚基的直接相互作用发生的，但哺乳动物神经元中L型钙通道增强的信号转导途径仍然未知。在本研究中，在存在蛋白激酶A（PKA）和蛋白激酶C（PKC）途径的各种调节剂的情况下，在出生后第6-8天大鼠海马的急性培养物中引发钙电流。用Gi/o抑制剂（百日咳毒素，200 ng/ml）过夜处理可消除GABAB激动剂巴氯芬（10 μM）对钙电流的衰减，而对钙电流的增强无影响。这些数据表明，虽然N型钙电流的衰减是由G蛋白的Gi/o亚型介导的，但L型钙电流的增强需要不同的G蛋白的激活。巴氯芬对钙电流持续成分的增强作用被PKC抑制剂GF-109203 X（500 nM）、氯化白屈菜红碱（5 μM）和PKC片段19-36（2 μM）阻断，并被PKC激活剂佛波醇-12-肉豆蔻酸酯-13-乙酸酯（1 μM）模拟。PKA抑制剂H-89（1 μM）和PKA片段6-22（500 nM）可阻断钙电流持续成分的增强，但Rp-cAMPS（30 μM）不能阻断，PKA激活剂8-Br-cAMP（500 μM - 1 mM）也不能模拟这种增强。这些数据表明，单独激活PKC足以增强L型钙电流，但PKA也可能参与GABAB受体介导的效应。
In the early neonatal period activation of GABAB receptors attenuates calcium current through N-type calcium channels while enhancing current through L-type calcium channels in rat hippocampal neurons. The attenuation of N-type calcium current has been previously demonstrated to occur through direct interactions of the βγ subunits of Gi/o G-proteins, but the signal transduction pathway for the enhancement of L-type calcium channels in mammalian neurons remains unknown. In the present study, calcium currents were elicited in acute cultures from postnatal day 6–8 rat hippocampi in the presence of various modulators of protein kinase A (PKA) and protein kinase C (PKC) pathways. Overnight treatment with an inhibitor of Gi/o (pertussis toxin, 200 ng/ml) abolished the attenuation of calcium current by the GABAB agonist, baclofen (10 μM) with no effect on the enhancement of calcium current. These data indicate that while the attenuation of N-type calcium current is mediated by the Gi/o subtype of G-protein, the enhancement of L-type calcium current requires activation of a different G-protein. The enhancement of the sustained component of calcium current by baclofen was blocked by PKC inhibitors, GF-109203X (500 nM), chelerythrine chloride (5 μM), and PKC fragment 19–36 (2 μM) and mimicked by the PKC activator phorbol-12-myristate-13-acetate (1 μM). The enhancement of the sustained component of calcium current was blocked by PKA inhibitors H-89 (1 μM) and PKA fragment 6–22 (500 nM) but not Rp-cAMPS (30 μM) and it was not mimicked by the PKA activator, 8-Br-cAMP (500 μM – 1 mM). The data suggest that activation of PKC alone is sufficient to enhance L-type calcium current but that PKA may also be involved in the GABAB receptor mediated effect.
登录
查看更多内容
影响因子：
4.8
作者：
Furukawa, T;Miura, R;Nukada, T
通讯作者：
Nukada, T
影响因子：
3
作者：
Bray, Jennifer G.;Mynlieff, Michelle
通讯作者：
Mynlieff, Michelle
影响因子：
4.7
作者：
Ko, Michael L.;Liu, Yilin;Ko, Gladys Y. -P.
通讯作者：
Ko, Gladys Y. -P.
影响因子：
5.5
作者：
Harayama, N;Shibuya, I;Yamashita, H
通讯作者：
Yamashita, H
影响因子：
2.5
作者：
Greif, GJ;Sodickson, DL;Mende, U
通讯作者：
Mende, U