EVIDENCE THAT NEURONAL G-PROTEIN-GATED INWARDLY RECTIFYING K+ CHANNELS ARE ACTIVATED BY G-BETA-GAMMA SUBUNITS AND FUNCTION AS HETEROMULTIMERS
EVIDENCE THAT NEURONAL G-PROTEIN-GATED INWARDLY RECTIFYING K+ CHANNELS ARE ACTIVATED BY G-BETA-GAMMA SUBUNITS AND FUNCTION AS HETEROMULTIMERS
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DOI：
10.1073/pnas.92.14.6542
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发表时间：
1995-07-03
影响因子：
11.1
通讯作者：
LESTER, HA
中科院分区：
文献类型：
--
作者：
KOFUJI, P;DAVIDSON, N;LESTER, HA
鸟嘌呤核苷酸结合蛋白（G蛋白）激活心脏心房细胞中的K+电导以减慢心率，并激活神经元中的K+电导以降低兴奋性。最近从心脏（GIRK 1/Kir 3.1）和脑cDNA文库（GIRK 2/Kir 3.2和GIRK 3/Kir 3.3）中克隆了编码G蛋白偶联的内向整流钾离子通道（GIRK）的三种亚型的cDNA。在这里，我们报道了在非洲爪蟾卵母细胞中，GIRK 2而不是GIRK 3可以被G蛋白亚基G β（1）和G γ（2）激活。此外，当GIRK 3或GIRK 2与GIRK 1共表达并被毒蕈碱受体或G β γ亚基激活时，G蛋白介导的内向电流增加了5至40倍。GIRK 1 + GIRK 2共表达的单通道电导介于GIRK 1单独和GIRK 2单独之间，共表达通道的电压跳跃动力学显示了新的动力学特性。另一方面，GIRK 3与GIRK 2的共表达抑制了GIRK 2单独的反应。这些研究表明，涉及几个GIRKs的异源多聚体的形成是神经递质偶联的内向整流性K+通道的表达水平和功能产生多样性的重要机制。
Guanine nucleotide-binding proteins (G proteins) activate K+ conductances in cardiac atrial cells to slow heart rate and in neurons to decrease excitability. cDNAs encoding three isoforms of a G-protein-coupled, inwardly rectifying K+ channel (GIRK) have recently been cloned from cardiac (GIRK1/Kir 3.1) and brain cDNA libraries (GIRK2/Kir 3.2 and GIRK3/Kir 3.3). Here we report that GIRK2 but not GIRK3 can be activated by G protein subunits G beta(1) and G gamma(2) in Xenopus oocytes. Furthermore, when either GIRK3 or GIRK2 was coexpressed with GIRK1 and activated either by muscarinic receptors or by G beta gamma subunits, G-protein-mediated inward currents were increased by 5- to 40-fold. The single-channel conductance for GIRK1 plus GIRK2 coexpression was intermediate between those for GIRK1 alone and for GIRK2 alone, and voltage-jump kinetics for the coexpressed channels displayed new kinetic properties. On the other hand, coexpression of GIRK3 with GIRK2 suppressed the GIRK2 alone response. These studies suggest that formation of heteromultimers involving the several GIRKs is an important mechanism for generating diversity in expression level and function of neurotransmitter-coupled, inward rectifier K+ channels.