钾通道与癫痫_Journal of Epilepsy_The only official website

Authors：

 徐岚 ,  吴洵昳 , 唐兴华 , 洪震

复旦大学附属华山医院神经内科(上海，200040);

Corresponding author：

吴洵昳, Email: dr.xunyiwu@163.com

Keywords：

钾通道; 癫痫; 遗传

DOI：

10.7507/2096-0247.20160026

Video：

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离子通道是体内兴奋性调节的物质基础。其结构和/或功能异常，是癫痫的重要发病机制之一。钾通道是其中分布最广、类型最多的一类离子通道，目前已有多项研究证实钾通道与癫痫之间关系密切。现主要对钾通道结构与分类、钾通道异常及其相关的癫痫作一综述，从而为阐明癫痫的发病机制提供依据，为研制新型抗癫痫药物提供理论基础。

Citation： 徐岚, 吴洵昳, 唐兴华, 洪震. 钾通道与癫痫. Journal of Epilepsy, 2016, 2(2): 136-140. doi: 10.7507/2096-0247.20160026 Copy

1.	Meldrum BS, Rogawski MA. Molecular targets for antiepileptic drug development. Neurotherapeutics, 2007, 4(2): 18-61.
2.	Maljevic S, Lerche H. Potassium channels:areview of broadening therapeutic possibilities for neurological diseases.J Neurol, 2013, 260(20): 2201-2211.
3.	Armijo JA, Shushtarian M, Valdizan EM, et al. Ion channels and epilepsy. Curr Pharm Des, 2005, 11(3): 1975-2003.
4.	Su T, Cong WD, Long YS, et al. Altered expression of voltage-gated potassium channel 4.2 and voltage-gated potassium channel 4-interacting protein, and changes in intracellular calcium levels following lithium-pilocarpine-induced status epilepticus. Neuroscience, 2008,157(13): 566-576.
5.	Shah NH, Aizenman E. Voltage-gated potassium channels at the cross roads of neuronal function, ischemic tolerance, and neurodegeneration. Transl Stroke Res, 2014, 5(2): 38-58.
6.	Rajakulendran S, Schorge S, Kullmann DM, et al. Episodic ataxia type 1:aneuronal potassium channelopathy. Neurotherapeutics, 2007, 4(3): 258-266.
7.	Glasscock E, Yoo JW, Chen TT, et al. K_v 1.1 potassium channel deficiency reveals brain-driven cardiac dysfunction asacandidate mechanism for sudden unexplained death in epilepsy(SUDEP).J Neurosci, 2010, 30(11): 5167-5175.
8.	Southan AP, Robertson B. Patch-clamp recordings from cerebellar basket cell bodies and their presynaptic terminals reveal an asymmetric distribution of voltage-gated potassium channels.J Neurosci, 1998, 18(8): 948-955.
9.	Dodson PD, Billups B, Rusznck Z, et al. Presynaptic rat K_v 1.2 channels suppress synaptic terminal hyperexcitability following action potential invasion.J Physiol, 2003, 550(20): 27-33.
10.	Petersson S, Persson AS, Johansen JE, et al. Truncation of the Shaker-like voltage-gated potassium channel, K_v 1.1, causes megencephaly. EurJNeurosci, 2003, 18(4): 3231-3240.
11.	Brew HM, Hallows JL, Tempel BL. Hyperexcitability and reduced low threshold potassium currents in auditory neurons of mice lacking the channel subunit K_v 1.1.J Physiol, 2003, 548(31): 1-20.
12.	Rogawski MA. KCNQ2/KCNQ3 K⁺ channels and the molecular pathogenesis of epilepsy: implications for therapy. Trends Neurosc, 2000, 23(12): 393-398.
13.	Cooper EC, Jan LY. M-channels: neurological diseases, neuromodulation, and drug development. Arch Neurol, 2003, 60(8): 496-500.
14.	Li H, Li N, Shen L,et al.Anovel mutation of KCNQ3 gene inaChinese family with benign familial neonatal convulsions. Epilepsy Res, 2008, 79(10): 1-5.
15.	Maljevic S, Lerche H. Potassium channel genes and benign familial neonatal epilepsy. Prog Brain Res, 2014, 213(20): 17-53.
16.	Miceli F, Soldovieri MV, Ambrosino P, et al. Early-onset epileptic encephalopathy caused by gain-of-function mutations in the voltage sensor of K_v7.2 and K_v7.3 potassium channel subunits.J Neurosci, 2015, 35(9): 3782-3793.
17.	Zhang X, Bertaso F, Yoo JW, et al. Deletion of the potassium channel K_v12.2 causes hippocampal hyperexcitability and epilepsy. Nat Neurosci, 2010,13(3): 1056-1058.
18.	Butt AM, Kalsi A. Inwardly rectifying potassium channels (K_ir) in central nervous system glia:aspecial role for K_ir4.1 in glial functions.J Cell Mol Med, 2006,10(7): 33-44.
19.	Chioza B, Osei-Lah A, Wilkie H, et al.Suggestive evidence for association of two potassium channel genes with different idiopathic generalised epilepsy syndromes. Epilepsy Res, 2002, 52(9): 107-116.
20.	Kobayashi T, Ikeda K.Gprotein-activated inwardly rectifying potassium channels as potential therapeutic targets. Curr Pharm Des, 2006, 12(5): 4513-4523.
21.	Buono RJ, Lohoff FW, Sander T, et al. Association between variation in the human KCNJ10 potassium ion channel gene and seizure susceptibility. Epilepsy Res, 2004, 58(12): 175-183.
22.	Proks P, Girard C, Haider S, et al.Agating mutation at the internal mouth of the K_ir6.2 pore is associated with DEND syndrome. Embo Rep, 2005, 6(1): 470-475.
23.	Hinterkeuser S, Schroder W, Hager G, et al. Astrocytes in the hippocampus of patients with temporal lobe epilepsy display changes in potassium conductances. EurJNeurosci, 2000, 12(5): 2087-2096．.
24.	Xu L, Hao Y, Wu X, et al. Tenidap, an agonist of the inwardly rectifying K⁺ channel K_ir2.3, delays the onset of cortical epileptiform activity inamodel of chronic temporal lobe epilepsy. Neurol Res, 2013, 35(7): 561-567.
25.	N’Gouemo P. Targeting BK (big potassium) channels in epilepsy. Expert Opin Ther Targets, 2011, 15(4): 1283-1295.
26.	Matire M, Barrese V, D’Amico M, et al. Presynaptic BK channels selectively control glutamate versus GABA release from cortical and hippocampal nerve terminals.J Neurochem, 2010, 115(13): 411-422.
27.	Du W, Bautista JF, Yang H, et al. Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder. Nat Genet, 2005, 37(6): 733-738.
28.	Lappin SC, Dale TJ, Brown JT, et al. Activation of SK channels inhibits epileptiform bursting in hippocampal CA3 neurons. Brain Res, 2005,1065(20): 37-46.
29.	Garduño J, Galván E, Fernández de Sevilla D, et al. 1-Ethyl-2-benzimidazolinone (EBIO) suppresses epileptiform activity in in vitro hippocampus. Neuropharmacology, 2005, 49(11): 376-388.
30.	Goldstein SA, Bayliss DA, Kim D, et al. International union of pharmacology LV nomenclature and molecular relationships of two-p potassium channels. Pharmacol Rev, 2005, 57(10): 527-540.
31.	Holter J, Carter D, Leresche N, et al.ATASK3 channel (KCNK9) mutation inagenetic model of absence epilepsy.J Mol Neurosci, 2005, 25(10): 37-51.
32.	Heilstedt HA, Burgess DL, Anderson AE, et al. Loss of the potassium channel beta-subunit gene, KCNAB2, is associated with epilepsy in patients with 1p36 deletion syndrome. Epilepsia, 2001, 42(7): 1103-1111.
33.	Porter RJ, Nohria V, Rundfeldt C. Retigabine. Neurotherapeutics, 2007, 4(1): 149-154.
34.	Gunthorpe MJ, Large CH, Sankar R. The mechanism of action of retigabine (ezogabine),afirst-in-class K⁺ channel opener for the treatment of epilepsy. Epilepsia, 2012, 53(8): 412-424.
35.	Peretz A, Degani N, Nachman R, et al. Meclofenamic acid and diclofenac, novel templates of KCNQ2/Q3 potassium channel openers, depress cortical neuron activity and exhibit anticonvulsant properties. Mol Pharmacol, 2005, 67(13): 1053-1066.
36.	Kasteleijn-Nolst Trenité DG, Biton V, French JA, et al. K_v 7 potassium channel activation with ICA-105665 reduces photoparoxysmal EEG responses in patients with epilepsy. Epilepsia, 2013, 54(12): 1437-1443.
37.	Kasteleijn-Nolst Trenité D, Brandt C, Mayer T, et al. Dose-dependent suppression of human photoparoxysmal response with the competitive AMPA/kainate receptor antagonist BGG492: Clear PK/PD relationship. Epilepsia, 2015, 56(6): 924-932.
38.	Sheehan JJ, Benedetti BL, Barth AL. Anticonvulsant effects of the BK-channel antagonist paxilline. Epilepsia, 2009, 50(9): 711-720.

1. Meldrum BS, Rogawski MA. Molecular targets for antiepileptic drug development. Neurotherapeutics, 2007, 4(2): 18-61.
2. Maljevic S, Lerche H. Potassium channels:areview of broadening therapeutic possibilities for neurological diseases.J Neurol, 2013, 260(20): 2201-2211.
3. Armijo JA, Shushtarian M, Valdizan EM, et al. Ion channels and epilepsy. Curr Pharm Des, 2005, 11(3): 1975-2003.
4. Su T, Cong WD, Long YS, et al. Altered expression of voltage-gated potassium channel 4.2 and voltage-gated potassium channel 4-interacting protein, and changes in intracellular calcium levels following lithium-pilocarpine-induced status epilepticus. Neuroscience, 2008,157(13): 566-576.
5. Shah NH, Aizenman E. Voltage-gated potassium channels at the cross roads of neuronal function, ischemic tolerance, and neurodegeneration. Transl Stroke Res, 2014, 5(2): 38-58.
6. Rajakulendran S, Schorge S, Kullmann DM, et al. Episodic ataxia type 1:aneuronal potassium channelopathy. Neurotherapeutics, 2007, 4(3): 258-266.
7. Glasscock E, Yoo JW, Chen TT, et al. K_v 1.1 potassium channel deficiency reveals brain-driven cardiac dysfunction asacandidate mechanism for sudden unexplained death in epilepsy(SUDEP).J Neurosci, 2010, 30(11): 5167-5175.
8. Southan AP, Robertson B. Patch-clamp recordings from cerebellar basket cell bodies and their presynaptic terminals reveal an asymmetric distribution of voltage-gated potassium channels.J Neurosci, 1998, 18(8): 948-955.
9. Dodson PD, Billups B, Rusznck Z, et al. Presynaptic rat K_v 1.2 channels suppress synaptic terminal hyperexcitability following action potential invasion.J Physiol, 2003, 550(20): 27-33.
10. Petersson S, Persson AS, Johansen JE, et al. Truncation of the Shaker-like voltage-gated potassium channel, K_v 1.1, causes megencephaly. EurJNeurosci, 2003, 18(4): 3231-3240.
11. Brew HM, Hallows JL, Tempel BL. Hyperexcitability and reduced low threshold potassium currents in auditory neurons of mice lacking the channel subunit K_v 1.1.J Physiol, 2003, 548(31): 1-20.
12. Rogawski MA. KCNQ2/KCNQ3 K⁺ channels and the molecular pathogenesis of epilepsy: implications for therapy. Trends Neurosc, 2000, 23(12): 393-398.
13. Cooper EC, Jan LY. M-channels: neurological diseases, neuromodulation, and drug development. Arch Neurol, 2003, 60(8): 496-500.
14. Li H, Li N, Shen L,et al.Anovel mutation of KCNQ3 gene inaChinese family with benign familial neonatal convulsions. Epilepsy Res, 2008, 79(10): 1-5.
15. Maljevic S, Lerche H. Potassium channel genes and benign familial neonatal epilepsy. Prog Brain Res, 2014, 213(20): 17-53.
16. Miceli F, Soldovieri MV, Ambrosino P, et al. Early-onset epileptic encephalopathy caused by gain-of-function mutations in the voltage sensor of K_v7.2 and K_v7.3 potassium channel subunits.J Neurosci, 2015, 35(9): 3782-3793.
17. Zhang X, Bertaso F, Yoo JW, et al. Deletion of the potassium channel K_v12.2 causes hippocampal hyperexcitability and epilepsy. Nat Neurosci, 2010,13(3): 1056-1058.
18. Butt AM, Kalsi A. Inwardly rectifying potassium channels (K_ir) in central nervous system glia:aspecial role for K_ir4.1 in glial functions.J Cell Mol Med, 2006,10(7): 33-44.
19. Chioza B, Osei-Lah A, Wilkie H, et al.Suggestive evidence for association of two potassium channel genes with different idiopathic generalised epilepsy syndromes. Epilepsy Res, 2002, 52(9): 107-116.
20. Kobayashi T, Ikeda K.Gprotein-activated inwardly rectifying potassium channels as potential therapeutic targets. Curr Pharm Des, 2006, 12(5): 4513-4523.
21. Buono RJ, Lohoff FW, Sander T, et al. Association between variation in the human KCNJ10 potassium ion channel gene and seizure susceptibility. Epilepsy Res, 2004, 58(12): 175-183.
22. Proks P, Girard C, Haider S, et al.Agating mutation at the internal mouth of the K_ir6.2 pore is associated with DEND syndrome. Embo Rep, 2005, 6(1): 470-475.
23. Hinterkeuser S, Schroder W, Hager G, et al. Astrocytes in the hippocampus of patients with temporal lobe epilepsy display changes in potassium conductances. EurJNeurosci, 2000, 12(5): 2087-2096．.
24. Xu L, Hao Y, Wu X, et al. Tenidap, an agonist of the inwardly rectifying K⁺ channel K_ir2.3, delays the onset of cortical epileptiform activity inamodel of chronic temporal lobe epilepsy. Neurol Res, 2013, 35(7): 561-567.
25. N’Gouemo P. Targeting BK (big potassium) channels in epilepsy. Expert Opin Ther Targets, 2011, 15(4): 1283-1295.
26. Matire M, Barrese V, D’Amico M, et al. Presynaptic BK channels selectively control glutamate versus GABA release from cortical and hippocampal nerve terminals.J Neurochem, 2010, 115(13): 411-422.
27. Du W, Bautista JF, Yang H, et al. Calcium-sensitive potassium channelopathy in human epilepsy and paroxysmal movement disorder. Nat Genet, 2005, 37(6): 733-738.
28. Lappin SC, Dale TJ, Brown JT, et al. Activation of SK channels inhibits epileptiform bursting in hippocampal CA3 neurons. Brain Res, 2005,1065(20): 37-46.
29. Garduño J, Galván E, Fernández de Sevilla D, et al. 1-Ethyl-2-benzimidazolinone (EBIO) suppresses epileptiform activity in in vitro hippocampus. Neuropharmacology, 2005, 49(11): 376-388.
30. Goldstein SA, Bayliss DA, Kim D, et al. International union of pharmacology LV nomenclature and molecular relationships of two-p potassium channels. Pharmacol Rev, 2005, 57(10): 527-540.
31. Holter J, Carter D, Leresche N, et al.ATASK3 channel (KCNK9) mutation inagenetic model of absence epilepsy.J Mol Neurosci, 2005, 25(10): 37-51.
32. Heilstedt HA, Burgess DL, Anderson AE, et al. Loss of the potassium channel beta-subunit gene, KCNAB2, is associated with epilepsy in patients with 1p36 deletion syndrome. Epilepsia, 2001, 42(7): 1103-1111.
33. Porter RJ, Nohria V, Rundfeldt C. Retigabine. Neurotherapeutics, 2007, 4(1): 149-154.
34. Gunthorpe MJ, Large CH, Sankar R. The mechanism of action of retigabine (ezogabine),afirst-in-class K⁺ channel opener for the treatment of epilepsy. Epilepsia, 2012, 53(8): 412-424.
35. Peretz A, Degani N, Nachman R, et al. Meclofenamic acid and diclofenac, novel templates of KCNQ2/Q3 potassium channel openers, depress cortical neuron activity and exhibit anticonvulsant properties. Mol Pharmacol, 2005, 67(13): 1053-1066.
36. Kasteleijn-Nolst Trenité DG, Biton V, French JA, et al. K_v 7 potassium channel activation with ICA-105665 reduces photoparoxysmal EEG responses in patients with epilepsy. Epilepsia, 2013, 54(12): 1437-1443.
37. Kasteleijn-Nolst Trenité D, Brandt C, Mayer T, et al. Dose-dependent suppression of human photoparoxysmal response with the competitive AMPA/kainate receptor antagonist BGG492: Clear PK/PD relationship. Epilepsia, 2015, 56(6): 924-932.
38. Sheehan JJ, Benedetti BL, Barth AL. Anticonvulsant effects of the BK-channel antagonist paxilline. Epilepsia, 2009, 50(9): 711-720.

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