A regenerative link in the ionic fluxes through the weaver potassium channel underlies the pathophysiology of the mutation.
A regenerative link in the ionic fluxes through the weaver potassium channel underlies the pathophysiology of the mutation.
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通过韦弗钾通道的离子通量的再生联系是突变病理生理学的基础。
DOI：
10.1073/pnas.93.26.15429
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发表时间：
1996
影响因子：
11.1
通讯作者：
Lester,HA
中科院分区：
文献类型：
--
作者：
Silverman,SK;Kofuji,P;Dougherty,DA;Davidson,N;Lester,HA
纯合子织鼠在几个脑区显示神经元变性。先前在异源表达系统中的实验表明，G蛋白门控的内向整流K+通道（GIRK2）携带织孔区GYG-to-SYG突变(i)不被Gβγ亚基激活，而是表现出组成性激活，（ii）不再是K+选择性通道，但也传导Na+。目前关于weavergirk2 （wvGIRK2）在异种卵母细胞中表达的实验表明，组成激活的水平取决于细胞内Na+浓度。特别是，降低细胞内Na+的操作会产生通过G蛋白途径激活的Na+可渗透电流成分。因此，本构激活可能不会出现，因为编织突变直接改变了通道蛋白的门控转变。相反，可能存在Na+通过wvgirk2通道内流的再生循环，导致额外的Na+激活。我们还表明，wvgirk2通道可渗透到Ca2+，为weaverphenotype特征的变性提供了额外的机制。我们进一步证明，具有类似编织突变的GIRK4通道具有与wvgirk2通道相似的特性，从而提供了在几乎所有已知的K+通道中维持GYG序列的选择压力的一瞥。
The homozygousweavermouse displays neuronal degeneration in several brain regions. Previous experiments in heterologous expression systems showed that the G protein-gated inward rectifier K+channel (GIRK2) bearing theweaverpore-region GYG-to-SYG mutation (i) is not activated by Gβγsubunits, but instead shows constitutive activation, and (ii) is no longer a K+-selective channel but conducts Na+as well. The present experiments onweaverGIRK2 (wvGIRK2) expressed inXenopusoocytes show that the level of constitutive activation depends on intracellular Na+concentration. In particular, manipulations that decrease intracellular Na+produce a component of Na+-permeable current activated via a G protein pathway. Therefore, constitutive activation may not arise because theweavermutation directly alters the gating transitions of the channel protein. Instead, there may be a regenerative cycle of Na+influx through thewvGIRK2 channel, leading to additional Na+activation. We also show that thewvGIRK2 channel is permeable to Ca2+, providing an additional mechanism for the degeneration that characterizes theweaverphenotype. We further demonstrate that the GIRK4 channel bearing the analogousweavermutation has properties similar to those of thewvGIRK2 channel, providing a glimpse of the selective pressures that have maintained the GYG sequence in nearly all known K+channels.
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异聚通道形成和无 Ca2+ 培养基可降低 Weaver Kir 3.2 等位基因的毒性作用
影响因子：
3.5
作者：
S. Tucker;M. Pessia;A. Moorhouse;F. Gribble;F. Ashcroft;J. Maylie;J. Adelman
通讯作者：
J. Adelman
编织颗粒神经元被钙通道拮抗剂和针对层粘连蛋白B2链神经突生长结构域的抗体挽救。
影响因子：
7.8
作者：
Liesi, P;Wright, JM
通讯作者：
Wright, JM
影响因子：
3.4
作者：
HEGINBOTHAM, L;LU, Z;MACKINNON, R
通讯作者：
MACKINNON, R
影响因子：
16.2
作者：
WEI, A;SOLARO, C;SALKOFF, L
通讯作者：
SALKOFF, L
影响因子：
3.8
作者：
Hartzell, HC
通讯作者：
Hartzell, HC