Direct G‐Protein Regulation of Ca2+ Channels
Direct G‐Protein Regulation of Ca2+ Channels
复制标题
G 蛋白对 Ca2+ 通道的直接调节
DOI：
--
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发表时间：
1989
影响因子：
5.2
通讯作者：
L. Birnbaumer
中科院分区：
文献类型：
--
作者：
A. Brown;A. Yatani;Y. Imoto;J. Codina;R. Mattera;L. Birnbaumer
当我们第一次确定特异性鸟嘌呤核苷酸结合或G蛋白可以直接门控毒蕈碱胆碱能心房K+通道时，我们想知道这种现象有多普遍。如果其他组织中的K+通道也能像毒蕈碱心房K+通道一样被神经递质或激素以非环磷酸腺苷（cAMP）依赖的方式激活，则它们是主要的候选者。当我们发现在心脏中有效的相同的外源性G蛋白G1模仿生长抑素和乙酰胆碱对克隆垂体前叶细胞系GH 3细胞中特异性K+通道的作用时，我们的期望得到了证实。GH 3钾离子通道的电导比心房钾离子通道的电导大，这表明G蛋白的直接门控并不局限于一种类型的钾离子通道，这鼓励我们通过询问是否可能涉及完全不同类型的通道来扩大我们的研究范围。我们转向Caz+通道的原因如下：（1）三磷酸鸟苷（GTP）改变了心脏肌膜和骨骼肌t-小管中二氢吡啶（DHP）的结合;（2）G蛋白参与了多种神经递质与Caz+通道的偶联7 *; G蛋白偶联阿片受体和Caz+通道。DHP敏感性Ca 2+通道的情况更复杂，因为它们也受第二信使调节（图1），并且当确定直接途径的存在时，必须排除这种机制。心脏和骨骼肌是令人满意的组织，因为至少有三种类型的百日咳毒素（PTX）底物和两种类型的霍乱（CTX）底物已被报道用于心脏肌膜，并且在骨骼肌t-小管中发现了两种类型的PTX和CTX底物。“我们发现G蛋白可以直接门控心脏中DHP敏感的Ca 2+通道。和骨骼肌16，并且我们使用重组DNA技术证明了单个G蛋白G1，如此命名是因为它是腺苷酸环化酶的刺激调节剂，也可以门控Ca 2+通道。'~'~
When we first identified specific guanine nucleotide binding, or G proteins, that could directly gate muscarinic cholinergic atrial K+ channels,'*z we wondered how widespread the phenomenon was. K+ channels in other tissues were prime candidates if they, like muscarinic atrial K+ channels, could also be activated by neurotransmitters or hormones in a cyclic adenosine 3',5'-cyclic monophosphate (CAMP)-independent manner. Our expectations were confirmed when we found that the same exogenous G protein, G,, that was effective in heart mimicked the effects of somatostatin and acetylcholine on specific K+ channels in GH3 cells, a clonal anterior pituitary cell line.',' The GH3 K+ channels had a larger conductance than the atrial K+ channels indicating that direct gating by G proteins was not restricted to one type of K+ channel and this encouraged us to broaden the scope of our enquiry by asking whether a completely different category of channels might be involved. We turned to Caz+ channels for the following reasons: ( 1) guanosine triphosphate (GTP)-altered dihydropyridine (DHP) binding in cardiac sarcolemmal and skeletal muscle t-tubule (2) G proteins were implicated in the coupling of a variety of neurotransmitters to Caz+ channels7.*; and (3) G proteins were shown to couple opioid receptors to Caz+ channel^.^ The situation for DHP-sensitive Ca2+ channels is more complicated because they are also modulated by second messengers (FIG. l) , and this mechanism has to be excluded when the presence of direct pathways is being determined. Heart and skeletal muscle were satisfactory tissues because at least three types of pertussis toxin (PTX) s~bs t r a t e l~" and two types of cholera (CTX) substrate" have been reported for cardiac sarcolemma, and two types of PTX and CTX substrates have been found in skeletal muscle t-tubules." We found that G proteins could directly gate DHP-sensitive Ca2+ channels in heart"." and skeletal muscle16 and we proved, using recombinant DNA techniques, that a single G protein, G,, so named because it is the stimulatory regulator of adenylyl cyclase, could also gate Caz+ channel~. '~'~
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影响因子：
56.9
作者：
JM Caffrey;AM Brown;Schneider
通讯作者：
JM Caffrey;AM Brown;Schneider
Ns 和 Ni，腺苷酸环化酶的刺激性和抑制性调节成分。
DOI：
--
发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Codina,J;Hildebrandt,JD;Sekura,RD;Birnbaumer,M;Bryan,J;Manclark,CR;Iyengar,R;Birnbaumer,L
通讯作者：
Birnbaumer,L
G 蛋白与离子通道的直接偶联。
DOI：
10.1101/sqb.1988.053.01.044
发表时间：
1988
期刊：
Cold Spring Harbor symposia on quantitative biology
影响因子：
--
作者：
Brown,AM;Yatani,A;Imoto,Y;Kirsch,G;Hamm,H;Codina,J;Mattera,R;Birnbaumer,L
通讯作者：
Birnbaumer,L
DOI：
10.1073/pnas.82.4.1074
发表时间：
1985-01-01
影响因子：
11.1
作者：
TABOR, S;RICHARDSON, CC
通讯作者：
RICHARDSON, CC
鸡胚胎发育过程中心肌毒蕈碱受体的生理反应性和鸟嘌呤核苷酸敏感性的个体发生。
影响因子：
2.9
作者：
Halvorsen,SW;Nathanson,NM
通讯作者：
Nathanson,NM