Altered regulation of potassium and calcium channels by GABAB and adenosine receptors in hippocampal neurons from mice lacking Gαo
Altered regulation of potassium and calcium channels by GABAB and adenosine receptors in hippocampal neurons from mice lacking Gαo
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DOI：
10.1152/jn.2000.83.2.1010
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发表时间：
2000-02-01
影响因子：
2.5
通讯作者：
Mende, U
中科院分区：
文献类型：
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作者：
Greif, GJ;Sodickson, DL;Mende, U
在缺乏Gα(O)的小鼠海马神经元上，GABA(B)和腺苷受体改变了钾和钙通道的调节。J.神经生理素。83：1010-1018,2000。为了研究G(O)在神经递质受体对离子通道的调节中的作用，我们研究了两种Gα(O)亚型缺失的小鼠海马CA3区神经元离子电流的调节。在Gα(O)(-/-)小鼠的CA3神经元上，2-氯腺苷和GABA(B)受体激动剂巴氯芬激活内向整流钾电流并抑制电压依赖性钙电流，与Gα(O)(+/+)小鼠一样有效。然而，在Gα(O)(-/-)小鼠中，递质作用的动力学发生了显著的变化，因为激动剂的恢复要慢得多。例如，Gα(O)(+/+)小鼠神经元从2-氯腺苷抑制钙电流的恢复[时间常数为12.0+/-0.8(SE)S]比GA-O(+/+)小鼠神经元(时间常数为2.6+/-0.2 S)慢四倍以上。从巴氯芬效应中恢复过来也受到了类似的影响。在对照组小鼠神经元上，巴氯芬和2-氯腺苷对钙电流和钾电流的影响均可被短暂暴露于N-乙基马来酰亚胺(NEM)所消除。在缺乏Gα(O)的神经元中，经NEM处理后，巴氯芬对钙电流仍有一定的抑制作用，而巴氯芬对钾电流的激活和2-氯腺苷的这两种作用均被取消。这些结果表明，海马神经元上G蛋白偶联受体对Ca~(2+)和K~+电流的调节对Gα(O)没有绝对的要求。然而，在没有Gα(O)的情况下，调制发生了变化，具有慢得多的恢复动力学。一种可能的可能性是，非常丰富的Gα(O)通常被使用，但当缺乏时，很容易被具有不同性质的G蛋白所取代。
Altered regulation of potassium and calcium channels by GABA(B) and adenosine receptors in hippocampal neurons from mice lacking G alpha(o). J. Neurophysiol. 83: 1010-1018, 2000. To examine the role of G(o) in modulation of ion channels by neurotransmitter receptors, we characterized modulation of ionic currents in hippocampal CA3 neurons from mice lacking both isoforms of G alpha(o). In CA3 neurons from G alpha(o)(-/-) mice, 2-chloro-adenosine and the GABA(B)-receptor agonist baclofen activated inwardly rectifying K+ currents and inhibited voltage-dependent Ca2+ currents just as effectively as in G alpha(o)(+/+) littermates. However, the kinetics of transmitter action were dramatically altered in G alpha(o)(-/-) mice in that recovery on washout of agonist was much slower. For example, recovery from 2-chloro-adenosine inhibition of calcium current was more than fourfold slower in neurons from G alpha(o)(+/+) mice [time constant of 12.0 +/- 0.8 (SE) s] than in neurons from Ga-o(+/+) mice (time constant of 2.6 +/- 0.2 s). Recovery from baclofen effects was affected similarly. In neurons from control mice, effects of both baclofen and 2-chloro-adenosine on Ca2+ currents and K+ currents were abolished by brief exposure to external N-ethyl-maleimide (NEM). In neurons lacking G alpha(o), some inhibition of Ca2+ currents by baclofen remained after NEM treatment, whereas baclofen activation of K+ currents and both effects of 2-chloro-adenosine were abolished. These results show that modulation of Ca2+ and K+ currents by G protein-coupled receptors in hippocampal neurons does not have an absolute requirement for G alpha(o). However, modulation is changed in the absence of G alpha(o) in having much slower recovery kinetics. A likely possibility is that the very abundant G alpha(o) is normally used but, when absent, can readily be replaced by G proteins with different properties.