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GIRK2 剪接变异体和神经元 G 蛋白门控钾通道：对通道功能和行为的影响。

GIRK2 splice variants and neuronal G protein-gated K channels: implications for channel function and behavior.

机构信息

University of Minnesota, Department of Pharmacology, Minneapolis, MN, 55455, USA.

National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA.

出版信息

Sci Rep. 2017 May 9;7(1):1639. doi: 10.1038/s41598-017-01820-2.

DOI:10.1038/s41598-017-01820-2
PMID:28487514
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5431628/
Abstract

Many neurotransmitters directly inhibit neurons by activating G protein-gated inwardly rectifying K (GIRK) channels, thereby moderating the influence of excitatory input on neuronal excitability. While most neuronal GIRK channels are formed by GIRK1 and GIRK2 subunits, distinct GIRK2 isoforms generated by alternative splicing have been identified. Here, we compared the trafficking and function of two isoforms (GIRK2a and GIRK2c) expressed individually in hippocampal pyramidal neurons lacking GIRK2. GIRK2a and GIRK2c supported comparable somato-dendritic GIRK currents in Girk2 pyramidal neurons, although GIRK2c achieved a more uniform subcellular distribution in pyramidal neurons and supported inhibitory postsynaptic currents in distal dendrites better than GIRK2a. While over-expression of either isoform in dorsal CA1 pyramidal neurons restored contextual fear learning in a conditional Girk2 mouse line, GIRK2a also enhanced cue fear learning. Collectively, these data indicate that GIRK2 isoform balance within a neuron can impact the processing of afferent inhibitory input and associated behavior.

摘要

许多神经递质通过激活 G 蛋白门控内向整流钾 (GIRK) 通道直接抑制神经元，从而调节兴奋性输入对神经元兴奋性的影响。虽然大多数神经元 GIRK 通道由 GIRK1 和 GIRK2 亚基组成，但已经确定通过选择性剪接产生了不同的 GIRK2 同工型。在这里，我们比较了在缺乏 GIRK2 的海马锥体神经元中单独表达的两种同工型（GIRK2a 和 GIRK2c）的运输和功能。GIRK2a 和 GIRK2c 在 Girk2 锥体神经元中支持可比的体树突 GIRK 电流，尽管 GIRK2c 在锥体神经元中实现了更均匀的亚细胞分布，并比 GIRK2a 更好地支持远端树突的抑制性突触后电流。虽然在背侧 CA1 锥体神经元中过表达任一同型都能恢复条件性 Girk2 小鼠系的情境恐惧学习，但 GIRK2a 也增强了线索恐惧学习。总的来说，这些数据表明神经元内 GIRK2 同工型的平衡可以影响传入抑制性输入的处理和相关行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7b1/5431628/d4a5658a3d26/41598_2017_1820_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7b1/5431628/1dad0a533f9b/41598_2017_1820_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7b1/5431628/27eef347aa09/41598_2017_1820_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7b1/5431628/7316726b4c19/41598_2017_1820_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7b1/5431628/36d6dc3e65c7/41598_2017_1820_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7b1/5431628/51aa568ac326/41598_2017_1820_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7b1/5431628/03e2b910f198/41598_2017_1820_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7b1/5431628/d4a5658a3d26/41598_2017_1820_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7b1/5431628/1dad0a533f9b/41598_2017_1820_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7b1/5431628/27eef347aa09/41598_2017_1820_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7b1/5431628/7316726b4c19/41598_2017_1820_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7b1/5431628/36d6dc3e65c7/41598_2017_1820_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7b1/5431628/51aa568ac326/41598_2017_1820_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7b1/5431628/03e2b910f198/41598_2017_1820_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7b1/5431628/d4a5658a3d26/41598_2017_1820_Fig7_HTML.jpg

相似文献

[1]
GIRK2 splice variants and neuronal G protein-gated K channels: implications for channel function and behavior.

Sci Rep. 2017-5-9

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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引用本文的文献

[1]
Domain-selective and sex-dependent regulation of learning and memory in mice by GIRK channel activity in CA1 pyramidal neurons of the dorsal hippocampus.

Learn Mem. 2024-9

[2]
Amyloid-β oligomers trigger sex-dependent inhibition of GIRK channel activity in hippocampal neurons in mice.

Sci Signal. 2024-10

[3]
GIRK2 Channels in Down Syndrome and Alzheimer's Disease.

Curr Alzheimer Res. 2022

[4]
Spatial Memory Training Counteracts Hippocampal GIRK Channel Decrease in the Transgenic APP J9 Alzheimer's Disease Mouse Model.

Int J Mol Sci. 2022-11-3

[5]
Alcohol reverses the effects of KCNJ6 (GIRK2) noncoding variants on excitability of human glutamatergic neurons.

Mol Psychiatry. 2023-2

[6]
Enhanced GIRK2 channel signaling in Down syndrome: A feasible role in the development of abnormal nascent neural circuits.

Front Genet. 2022-9-12

[7]
Neuronal G protein-gated K channels.

Am J Physiol Cell Physiol. 2022-8-1

[8]
Spatiotemporal Regulation of Transcript Isoform Expression in the Hippocampus.

Front Mol Neurosci. 2021-7-8

[9]
Next-generation inward rectifier potassium channel modulators: discovery and molecular pharmacology.

Am J Physiol Cell Physiol. 2021-6-1

[10]
The antitussive cloperastine improves breathing abnormalities in a Rett Syndrome mouse model by blocking presynaptic GIRK channels and enhancing GABA release.

Neuropharmacology. 2020-10-1

本文引用的文献

[1]
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[2]
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G Protein-Gated K Channel Ablation in Forebrain Pyramidal Neurons Selectively Impairs Fear Learning.

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RGS7/Gβ5/R7BP complex regulates synaptic plasticity and memory by modulating hippocampal GABABR-GIRK signaling.

Elife. 2014-4-22

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