Agonist-dependent single channel current and gating in alpha4beta2delta and alpha1beta2gamma2S GABAA receptors.
Agonist-dependent single channel current and gating in alpha4beta2delta and alpha1beta2gamma2S GABAA receptors.
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依赖激动剂的单个通道电流和alpha4beta2delta和alpha1beta2gamma2s Gabaa受体中的单个通道电流和门控。
DOI：
10.1085/jgp.200709871
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发表时间：
2008-02
影响因子：
3.8
通讯作者：
Harrison, Neil L.
中科院分区：
文献类型：
--
作者：
Keramidas, Angelo;Harrison, Neil L.
γ-氨基丁酸A型受体（GABAAR）家族介导哺乳动物脑中的两种类型的抑制。相抑制由主要由α1、β2和γ2亚基组成的突触GABAAR介导，而强直抑制由α4/6、β2和δ亚基组成的突触外GABAAR介导。我们利用由外向外的膜斑电生理记录研究了重组α4β2δ和α1β2γ2S GABAARs对GABA和4，5，6，7-四氢异恶唑并[5，4-c]吡啶-3（2 H）-酮（THIP）的激活特性。快速激动剂应用实验表明，THIP在α4β2δ GABAAR（β = 1600 s−1）上产生的打开速率比在α1β2γ2S GABAAR（β = 460 s−1）上产生的打开速率更快，而GABA激活α1β2γ2S GABAAR（β = 1800 s−1）比α4β2δ GABAAR（β < 440 s−1）更快。对α1β2γ2S和α4β2δ GABAAR的单通道记录显示，当被GABA和低浓度THIP激活时，两个通道在−70 mV时都打开到主电导状态为1025 pS，而饱和浓度的THIP在两个通道上都引起1036 pS的开放。饱和浓度的GABA在α4β2δ GABAAR上引起短暂（<10 ms）的开放，爆发内开放概率低（PO <0.3），在α1β2γ2S GABAAR上引起至少两种“模式”的单通道爆发活动，持续约100 ms。最普遍的爆发模式的PO为1.00.7，并由具有三个打开和三个关闭状态的反应方案描述，而“高”PO模式（1.00.9）的特征在于两个关闭和三个打开状态。THIP在α4β2δ和α1β2γ2S GABAAR中引起的单通道活动表现为中等持续时间（约33 ms）的单个爆发群（PO = 0.4-0.5），可以用两种GABAAR的两个关闭和两个打开状态的方案来描述。我们的数据确定受体亚型特异性和激动剂特异性的其他动力学特性，包括单位电导。
The family of γ-aminobutyric acid type A receptors (GABAARs) mediates two types of inhibition in the mammalian brain. Phasic inhibition is mediated by synaptic GABAARs that are mainly comprised of α1, β2, and γ2 subunits, whereas tonic inhibition is mediated by extrasynaptic GABAARs comprised of α4/6, β2, and δ subunits. We investigated the activation properties of recombinant α4β2δ and α1β2γ2S GABAARs in response to GABA and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3(2H)-one (THIP) using electrophysiological recordings from outside-out membrane patches. Rapid agonist application experiments indicated that THIP produced faster opening rates at α4β2δ GABAARs (β ∼1600 s−1) than at α1β2γ2S GABAARs (β ∼ 460 s−1), whereas GABA activated α1β2γ2S GABAARs more rapidly (β ∼1800 s−1) than α4β2δ GABAARs (β < 440 s−1). Single channel recordings of α1β2γ2S and α4β2δ GABAARs showed that both channels open to a main conductance state of ∼25 pS at −70 mV when activated by GABA and low concentrations of THIP, whereas saturating concentrations of THIP elicited ∼36 pS openings at both channels. Saturating concentrations of GABA elicited brief (<10 ms) openings with low intraburst open probability (PO ∼ 0.3) at α4β2δ GABAARs and at least two “modes” of single channel bursting activity, lasting ∼100 ms at α1β2γ2S GABAARs. The most prevalent bursting mode had a PO of ∼0.7 and was described by a reaction scheme with three open and three shut states, whereas the “high” PO mode (∼0.9) was characterized by two shut and three open states. Single channel activity elicited by THIP in α4β2δ and α1β2γ2S GABAARs occurred as a single population of bursts (PO ∼0.4–0.5) of moderate duration (∼33 ms) that could be described by schemes containing two shut and two open states for both GABAARs. Our data identify kinetic properties that are receptor-subtype specific and others that are agonist specific, including unitary conductance.
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影响因子：
64.8
作者：
COBB, SR;BUHL, EH;SOMOGYI, P
通讯作者：
SOMOGYI, P
影响因子：
5.5
作者：
AUERBACH, A;LINGLE, CJ
通讯作者：
LINGLE, CJ
影响因子：
16.2
作者：
MACONOCHIE, DJ;ZEMPEL, JM;STEINBACH, JH
通讯作者：
STEINBACH, JH
影响因子：
16.2
作者：
JONES, MV;WESTBROOK, GL
通讯作者：
WESTBROOK, GL
影响因子：
7.3
作者：
Brown, N;Kerby, J;Wafford, KA
通讯作者：
Wafford, KA