Involvement of Large-conductance Ca2+-activated K+ Channels in the Synaptic Transmission in the Lateral Amygdala / 大电导钙依赖性钾通道参与调节杏仁核侧核突触传递

神经药理学报 ›› 2012, Vol. 2 ›› Issue (1): 10-19.

Involvement of Large-conductance Ca²⁺-activated K⁺ Channels in the Synaptic Transmission in the Lateral Amygdala / 大电导钙依赖性钾通道参与调节杏仁核侧核突触传递

GUO Yan-yan, QI Feng-yan, ZHAO Ming-gao

第四军医大学药学院药理学教研室，西安，710032，中国

出版日期:2012-02-26 发布日期:2013-05-06
通讯作者: 招明高，男，教授，博士生导师；研究方向：神经精神药理学；Tel：+86-29-84774552, E-mail：minggao@fmmu.edu.cn
作者简介:郭艳艳，女，硕士；研究方向：焦虑症的神经机制
基金资助:
国家自然科学基金项目（No.31070923, No.31271144）

Involvement of Large-conductance Ca²⁺-activated K⁺ Channels in the Synaptic Transmission in the Lateral Amygdala

GUO Yan-yan, QI Feng-yan, ZHAO Ming-gao

Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China

Online:2012-02-26 Published:2013-05-06
Contact: 招明高，男，教授，博士生导师；研究方向：神经精神药理学；Tel：+86-29-84774552, E-mail：minggao@fmmu.edu.cn
About author:郭艳艳，女，硕士；研究方向：焦虑症的神经机制
Supported by:
国家自然科学基金项目（No.31070923, No.31271144）

摘要/Abstract

摘要： 目的：大电导钙依赖性钾通道（Large-conductance Ca²⁺-activated K⁺channels, BK_Ca) 在与应激相关的杏仁核高度表达，但在神经网络调控中作用的报道有限。前期的研究发现小鼠急性应激可引起杏仁核BK_Ca表达降低，伴随动物焦虑样表现。本研究我们将考察BK_Ca通道在杏仁核侧核突触传递与可塑性中的作用。方法：本研究采用免疫组织化学、行为学、蛋白质电泳和电生理记录的方法研究BK_Ca通道的作用。结果：首先发现BK_Ca通道与锥体神经元和中间神经元标志物(分别为CaMKIIα与GAD-65)共表达；免疫共沉淀检测发现BK_Ca通道与NMDA受体NR2A和NR2B亚型组成异源性复合物；进一步研究发现，阻断BK_Ca通道可易化丘脑-杏仁核侧核通路突触长时程增强（long-term potentiation，LTP)。结论：上述结果表明BK_Ca通道在杏仁核突触可塑性诱导中具有重要作用。

关键词: 大电导钙依赖性钾通道, 突触可塑性, 杏仁核

Abstract: Objective: Large-conductance Ca²⁺-activated K⁺(BK_Ca) channels are highly expressed in the lateral amygdala (LA), which is involved in stress disorders, but the role of these BK_Ca in the neuronal circuits are poorly understood. In the previous study, we found a significant reduction in BK_Ca channel expression in the amygdala of mice undergoing acute stress, which was accompanied by anxiety-like behaviors. In this study, we focused on the role of BK_Ca channels in the synaptic transmission and plasticity in the lateral amygdala. Methods: Behavioral tests, western-blot analysis and electrophysiological recordings were performed. Results: First, we found the co-distribution of BK_Ca channels immunoreactively with glutamatergic neuronal marker CaMKIIα or interneuron marker GAD-65 in the LA. In addition, both NR2A and NR2B were co-localized with the BK_Ca channels and formed a heteroreceptor complex in the soma and dendrites of the amygdala neurons. Furthermore, block of the BK_Ca channels notably facilitated long-term potentiation (LTP) induction at the thalamo-LA synapse. Conclusion: BK_Ca channels play critical roles in the synaptic plasticity in the LA.

Key words: large-conductance Ca²⁺-activated K⁺ channels, synaptic plasticity, amygdala

中图分类号:

R338

GUO Yan-yan, QI Feng-yan, ZHAO Ming-gao. Involvement of Large-conductance Ca²⁺-activated K⁺ Channels in the Synaptic Transmission in the Lateral Amygdala / 大电导钙依赖性钾通道参与调节杏仁核侧核突触传递[J]. 神经药理学报, 2012, 2(1): 10-19.

GUO Yan-yan, QI Feng-yan, ZHAO Ming-gao. Involvement of Large-conductance Ca²⁺-activated K⁺ Channels in the Synaptic Transmission in the Lateral Amygdala[J]. Acta Neuropharmacologica, 2012, 2(1): 10-19.

参考文献

[1] Pankaj Sah. Ca(2+)-activated K+ currents in neurones: types, physiological roles and modulation[J]. Trends Neurosci, 1996, 19(4):150-154.

[2] Nicholas P Poolos, Daniel Johnston. Calcium-activated potassium conductances contribute to action potential repolarization at the soma but not the dendrites of hippocampal CA1 pyramidal neurons[J]. J Neurosci, 1999, 19(13):5205-5212.

[3] Juan Martinez-Pinna, Philip J Davies, Elspeth M McLachlan. Diversity of channels involved in Ca(2+) activation of K(+) channels during the prolonged AHP in guinea-pig sympathetic neurons[J]. J Neurophysiol, 2000, 84(3):1346-1354.

[4] E S Louise Faber, Pankaj Sah. Ca2+-activated K+ (BK) channel inactivation contributes to spike broadening during repetitive firing in the rat lateral amygdala [J]. J Physiol, 2003, 552(Pt 2):483-497.

[5] Womack MD, Hoang C, Khodakhah K. Large conductance calcium-activated potassium channels affect both spontaneous firing and intracellular calcium concentration in cerebellar Purkinje neurons[J]. Neuroscience, 2009, 162(4):989-1000.

[6] Haghdoost-Yazdi H, Janahmadi M, Behzadi G. Iberiotoxin-sensitive large conductance Ca2+ -dependent K+ (BK) channels regulate the spike configuration in the burst firing of cerebellar Purkinje neurons[J]. Brain Res, 2008, 1212:1-8.

[7] Lancaster B, Nicoll RA, Perkel DJ. Calcium activates two types of potassium channels in rat hippocampal neurons in culture[J]. J Neurosci, 1991, 11(1):23-30.

[8] Lee BC, Lim HH, Kim S, et al. Localization of a site of action for benzofuroindole-induced potentiation of BKCa channels[J]. Mol Pharmacol, 2012, 82(2):143-155.

[9] Shao Li-rong, Ragnhild Halvorsrud, Lyle Borg-Graham, et al. The role of BK-type Ca2+-dependent K+ channels in spike broadening during repetitive firing in rat hippocampal pyramidal cells[J]. J Physiol, 1999, 521 (Pt 1):135-146.

[10] Marianne R Smith, Alexandra B Nelson, Sascha Du Lac. Regulation of firing response gain by calcium-dependent mechanisms in vestibular nucleus neurons[J]. J Neurophysiol, 2002, 87(4):2031-2042.

[11] Sun Fang, Emiko Hayama, Yasuhiro Katsube, et al. The role of the large-conductance voltage-dependent and calcium-activated potassium (BK(Ca)) channels in the regulation of rat ductus arteriosus tone[J]. Heart Vessels, 2010, 25(6):556-564.

[12] Alexandra B Nelson, Claudia M Krispel, Chris Sekirnjak, et al. Long-lasting increases in intrinsic excitability triggered by inhibition[J]. Neuron, 2003, 40(3):609-620.

[13] Andrea L Meredith, Steven W Wiler, Brooke H Miller, et al. BK calcium-activated potassium channels regulate circadian behavioral rhythms and pacemaker output[J]. Nat Neurosci, 2006, 9(8):1041-1049.

[14] Edwin Santini, Gregory J Quirk, James T Porter. Fear conditioning and extinction differentially modify the intrinsic excitability of infralimbic neurons[J]. J Neurosci, 2008, 28(15):4028-4036.

[15] Elizabeth A Matthews, Aldis P Weible, Samit Shah, et al. The BK-mediated fAHP is modulated by learning a hippocampus-dependent task[J]. Proc Natl Acad Sci USA, 2008, 105(39):15154-15159.

[16] Guo YY, Liu SB, Cui GB, et al. Acute stress induces down-regulation of large-conductance Ca2+-activated potassium channels in the lateral amygdala[J]. J Physiol, 2012, 590(Pt 4):875-886.

[17] Bliss TV, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus[J]. Nature, 1993, 361(6407):31-39.

[18] Stephen Maren. Long-term potentiation in the amygdala: a mechanism for emotional learning and memory[J]. Trends Neurosci, 1999, 22(12):561-567.

[19] Zhao Ming-gao, Toyoda Hiroki, Lee Yong Seok, et al. Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory[J]. Neuron, 2005, 47(6):859-872.

[20] Jeffry S Isaacson, Gabe J Murphy. Glutamate-mediated extrasynaptic inhibition: direct coupling of NMDA receptors to Ca(2+)-activated K+ channels[J]. Neuron, 2001, 31(6):1027-1034.

[21] Wang Han-sen, Wu Long-jun, Susan S Kim, et al. FMRP acts as a key messenger for dopamine modulation in the forebrain[J]. Neuron, 2008, 59(4):634-647.

[22] Brewer G J, Torricelli J R, Evege E K, et al. Optimized survival of hippocampal neurons in B27-supplemented Neurobasal, a new serum-free medium combination[J]. J Neurosci Res, 1993, 35(5):567-576.

[23] Evgeny Tsvetkov, Ryong Moon Shin, Vadim Y Bolshakov. Glutamate uptake determines pathway specificity of long-term potentiation in the neural circuitry of fear conditioning[J]. Neuron, 2004, 41(1):139-151.

[24] Evgeny Tsvetkov, William A Carlezon, Francine M Benes, et al. Fear conditioning occludes LTP-induced presynaptic enhancement of synaptic transmission in the cortical pathway to the lateral amygdala[J]. Neuron, 2002, 34(2):289-300.

[25] Wu Long-jun, Shanelle W Ko, Hiroki Toyoda, et al. Increased anxiety-like behavior and enhanced synaptic efficacy in the amygdala of GluR5 knockout mice[J]. PLoS One, 2007, 2(1):e167.

[26] Mala M Shah, Dennis G Haylett. K+ currents generated by NMDA receptor activation in rat hippocampal pyramidal neurons[J]. J Neurophysiol, 2002, 87(6):2983-2989.

[27] Ko Shanelle, Zhao Ming-gao, Toyoda Hiroki, et al. Altered behavioral responses to noxious stimuli and fear in glutamate receptor 5 (GluR5)- or GluR6-deficient mice[J]. J Neurosci, 2005, 25(4):977-984.

[28] Roger A Nicoll, Robert C Malenka. Contrasting properties of two forms of long-term potentiation in the hippocampus[J]. Nature, 1995, 377(6545):115-118.

[29] Zalutsky R A, Nicoll R A. Comparison of two forms of long-term potentiation in single hippocampal neurons[J]. Science, 1990, 248(4963):1619-1624.

[30] Bernd Fakler, John P Adelman. Control of K(Ca) channels by calcium nano/microdomains[J]. Neuron, 2008, 59(6):873-881.

[31] Jeremy R Edgerton, Peter H Reinhart. Distinct contributions of small and large conductance Ca2+-activated K+ channels to rat Purkinje neuron function[J]. J Physiol, 2003, 548(Pt 1):53-69.

[32] Murali Prakriya, Christopher J Lingle. BK channel activation by brief depolarizations requires Ca2+ influx through L- and Q-type Ca2+ channels in rat chromaffin cells[J]. J Neurophysiol, 1999, 81(5):2267-2278.

[33] Andreas Muller, Maria Kukley, Mischa Uebachs, et al. Nanodomains of single Ca2+ channels contribute to action potential repolarization in cortical neurons[J]. J Neurosci, 2007, 27(3):483-495.

[34] Thu Jennifer Ngo-Anh, Brenda L Bloodgood, Michael Lin, et al. SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic spines[J]. Nat Neurosci, 2005, 8(5):642-649.

[35] Faber ES, Delaney AJ, Sah P. SK channels regulate excitatory synaptic transmission and plasticity in the lateral amygdala[J]. Nat Neurosci, 2005, 8(5):635-641.

[36] Robert Pawlak, Ana Maria Magarinos, Jerry Melchor, et al. Tissue plasminogen activator in the amygdala is critical for stress-induced anxiety-like behavior[J]. Nat Neurosci, 2003, 6(2):168-174.

[37] Ingrid Ehrlich, Yann Humeau, Francois Grenier, et al. Amygdala inhibitory circuits and the control of fear memory[J]. Neuron, 2009, 62(6):757-771.

[38] Jonathan C Gewirtz, Michael Davis. Second-order fear conditioning prevented by blocking NMDA receptors in amygdala[J]. Nature, 1997, 388(6641):471-474.

[39] Gregory J Quirk, Christopher Repa, Joseph E LeDoux. Fear conditioning enhances short-latency auditory responses of lateral amygdala neurons: parallel recordings in the freely behaving rat[J]. Neuron, 1995, 15(5):1029-1039.

Involvement of Large-conductance Ca²⁺-activated K⁺ Channels in the Synaptic Transmission in the Lateral Amygdala / 大电导钙依赖性钾通道参与调节杏仁核侧核突触传递

Involvement of Large-conductance Ca²⁺-activated K⁺ Channels in the Synaptic Transmission in the Lateral Amygdala

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 8

编辑推荐

Metrics

[1]	曾菊，程斌，程肖蕊，周文霞，张永祥. 基于LPS 诱导小鼠炎症模型的LW-AFC 抗炎作用研究[J]. 神经药理学报, 2018, 8(2): 49-49.
[2]	楚世峰，张均田. 一种新型的抗老年痴呆剂:左旋黄皮酰胺的化学、生物学活性和作用机制研究[J]. 神经药理学报, 2014, 4(6): 33-43.
[3]	王琦王弘凯冉建华. 神经系统中丝裂原活化蛋白激酶磷酸酶-1的研究进展[J]. 神经药理学报, 2014, 4(1): 58-64.
[4]	吴苗苗，李炜，董晓华，张丹参. 全身麻醉药与记忆的相关性[J]. 神经药理学报, 2013, 3(6): 48-56.
[5]	郭敏，李刚. 突触可塑性相关蛋白的研究进展[J]. 神经药理学报, 2013, 3(6): 57-64.
[6]	李炜, 李婷婷, 齐赛卿, 张癸荣. 快速眼球运动睡眠剥夺对记忆和突触可塑性的影响及其分子机制的研究进展[J]. 神经药理学报, 2013, 3(4): 47-57.
[7]	黄倩，楚世峰，连晓媛，张均田. 人参皂苷Rg1的抗抑郁作用及其作用机制[J]. 神经药理学报, 2013, 3(1): 1-11.
[8]	车慧, 杨宝峰, 艾静. MicroRNA在学习记忆功能障碍中的作用[J]. 神经药理学报, 2011, 1(4): 26-32.