Overexpression of KCNN4 channels in principal neurons produces an anti-seizure effect without reducing their coding ability

Drew L. Gene therapy targets epilepsy. Nature. 2018;564:S10–s11.

Article  CAS  PubMed  Google Scholar 

Bernard C. Treating Epilepsy with a Light Potassium Diet. Sci Transl Med. 2012;4:161fs40–161fs40.

Article  PubMed  Google Scholar 

Nikitin ES, Vinogradova LV. Potassium channels as prominent targets and tools for the treatment of epilepsy. Expert Opin Ther Targets. 2021;25:223–35.

Article  CAS  PubMed  Google Scholar 

Wykes RC, Heeroma JH, Mantoan L, Zheng K, MacDonald DC, Deisseroth K, et al. Optogenetic and potassium channel gene therapy in a rodent model of focal neocortical epilepsy. Sci Transl Med. 2012;4:161ra152.

Article  PubMed  PubMed Central  Google Scholar 

Snowball A, Chabrol E, Wykes RC, Shekh-Ahmad T, Cornford JH, Lieb A, et al. Epilepsy Gene Therapy Using an Engineered Potassium Channel. J Neurosci. 2019;39:3159–69.

Article  PubMed  PubMed Central  Google Scholar 

Magloire V, Cornford J, Lieb A, Kullmann DM, Pavlov I. KCC2 overexpression prevents the paradoxical seizure-promoting action of somatic inhibition. Nat Commun. 2019;10:1225.

Article  PubMed  PubMed Central  Google Scholar 

Agostinho AS, Mietzsch M, Zangrandi L, Kmiec I, Mutti A, Kraus L, et al. Dynorphin-based “release on demand” gene therapy for drug-resistant temporal lobe epilepsy. EMBO Mol Med. 2019;11:e9963.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Qiu Y, O’Neill N, Maffei B, Zourray C, Almacellas-Barbanoj A, Carpenter JC, et al. On-demand cell-autonomous gene therapy for brain circuit disorders. Science (New York, N.Y.). 2022;378:523–32.

Article  CAS  PubMed  Google Scholar 

Kohling R, Wolfart J. Potassium Channels in Epilepsy. Cold Spring Harb Perspect Med. 2016;6:a022871.

Masnada S, Hedrich UBS, Gardella E, Schubert J, Kaiwar C, Klee EW, et al. Clinical spectrum and genotype-phenotype associations of KCNA2-related encephalopathies. Brain. 2017;140:2337–54.

Article  PubMed  Google Scholar 

Muona M, Berkovic SF, Dibbens LM, Oliver KL, Maljevic S, Bayly MA, et al. A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy. Nat Genet. 2015;47:39–46.

Article  CAS  PubMed  Google Scholar 

Singh B, Ogiwara I, Kaneda M, Tokonami N, Mazaki E, Baba K, et al. A Kv4.2 truncation mutation in a patient with temporal lobe epilepsy. Neurobiol Dis. 2006;24:245–53.

Article  CAS  PubMed  Google Scholar 

Corbett MA, Bellows ST, Li M, Carroll R, Micallef S, Carvill GL, et al. Dominant KCNA2 mutation causes episodic ataxia and pharmacoresponsive epilepsy. Neurology. 2016;87:1975–84.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Simons C, Rash LD, Crawford J, Ma L, Cristofori-Armstrong B, Miller D, et al. Mutations in the voltage-gated potassium channel gene KCNH1 cause Temple-Baraitser syndrome and epilepsy. Nat Genet. 2015;47:73–77.

Article  CAS  PubMed  Google Scholar 

Lee H, Lin MC, Kornblum HI, Papazian DM, Nelson SF. Exome sequencing identifies de novo gain of function missense mutation in KCND2 in identical twins with autism and seizures that slows potassium channel inactivation. Hum Mol Genet. 2014;23:3481–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Leo A, Citraro R, Constanti A, De Sarro G, Russo E. Are big potassium-type Ca(2+)-activated potassium channels a viable target for the treatment of epilepsy? Expert Opin Ther Targets. 2015;19:911–26.

Article  CAS  PubMed  Google Scholar 

Schorge S, Walker MC, Kullmann DM, Snowball A, Chabrol E. Expression vectors comprising engineered genes. WIPO (PCT). UK: Ucl Business Plc, 2018. (PCT) W, (ed).

Google Scholar 

Kole MH, Letzkus JJ, Stuart GJ. Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy. Neuron. 2007;55:633–47.

Article  CAS  PubMed  Google Scholar 

Foust AJ, Yu Y, Popovic M, Zecevic D, McCormick DA. Somatic membrane potential and Kv1 channels control spike repolarization in cortical axon collaterals and presynaptic boutons. J Neurosci. 2011;31:15490–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shu Y, Hasenstaub A, Duque A, Yu Y, McCormick DA. Modulation of intracortical synaptic potentials by presynaptic somatic membrane potential. Nature. 2006;441:761–5.

Article  CAS  PubMed  Google Scholar 

Roshchin MV, Matlashov ME, Ierusalimsky VN, Balaban PM, Belousov VV, Kemenes G, et al. A BK channel-mediated feedback pathway links single-synapse activity with action potential sharpening in repetitive firing. Sci Adv. 2018;4:eaat1357.

Article  PubMed  PubMed Central  Google Scholar 

King B, Rizwan AP, Asmara H, Heath NC, Engbers JD, Dykstra S, et al. IKCa channels are a critical determinant of the slow AHP in CA1 pyramidal neurons. Cell Rep. 2015;11:175–82.

Article  CAS  PubMed  Google Scholar 

Roshchin MV, Ierusalimsky VN, Balaban PM, Nikitin ES. Ca(2+)-activated KCa3.1 potassium channels contribute to the slow afterhyperpolarization in L5 neocortical pyramidal neurons. Sci Rep. 2020;10:14484.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tiwari MN, Mohan S, Biala Y, Yaari Y. Differential contributions of Ca(2+) -activated K(+) channels and Na(+) /K(+) -ATPases to the generation of the slow afterhyperpolarization in CA1 pyramidal cells. Hippocampus. 2018;28:338–57.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Guan D, Armstrong WE, Foehring RC. Electrophysiological properties of genetically identified subtypes of layer 5 neocortical pyramidal neurons: Ca(2)(+) dependence and differential modulation by norepinephrine. J Neurophysiol. 2015;113:2014–32.

Article  PubMed  PubMed Central  Google Scholar 

Vigneault P, Parent S, Kanda P, Michie C, Davis DR, Nattel S. Electrophysiological engineering of heart-derived cells with calcium-dependent potassium channels improves cell therapy efficacy for cardioprotection. Nat Commun. 2021;12:4963.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bulk E, Ay AS, Hammadi M, Ouadid-Ahidouch H, Schelhaas S, Hascher A, et al. Epigenetic dysregulation of KCa 3.1 channels induces poor prognosis in lung cancer. Int J Cancer. 2015;137:1306–17.

Article  CAS  PubMed  Google Scholar 

Turner KL, Honasoge A, Robert SM, McFerrin MM, Sontheimer H. A proinvasive role for the Ca(2+) -activated K(+) channel KCa3.1 in malignant glioma. Glia. 2014;62:971–81.

Article  PubMed  PubMed Central  Google Scholar 

Du Y, Song W, Chen J, Chen H, Xuan Z, Zhao L, et al. The potassium channel KCa3.1 promotes cell proliferation by activating SKP2 and metastasis through the EMT pathway in hepatocellular carcinoma. Int J Cancer. 2019;145:503–16.

Article  CAS  PubMed  Google Scholar 

Wang ZH, Shen B, Yao HL, Jia YC, Ren J, Feng YJ, et al. Blockage of intermediate-conductance-Ca(2+) -activated K(+) channels inhibits progression of human endometrial cancer. Oncogene. 2007;26:5107–14.

Article  CAS  PubMed  Google Scholar 

Nathanson JL, Yanagawa Y, Obata K, Callaway EM. Preferential labeling of inhibitory and excitatory cortical neurons by endogenous tropism of adeno-associated virus and lentivirus vectors. Neuroscience. 2009;161:441–50.

Article  CAS  PubMed  Google Scholar 

Franklin KBJ. The mouse brain in stereotaxic coordinates / Keith B.J. Franklin, George Paxinos. Amsterdam: Elsevier; 2008.

Google Scholar 

Aseyev N, Roshchin M, Ierusalimsky VN, Balaban PM, Nikitin ES. Biolistic delivery of voltage-sensitive dyes for fast recording of membrane potential changes in individual neurons in rat brain slices. J Neurosci Methods. 2013;212:17–27.

Article  PubMed  Google Scholar 

Ilin V, Malyshev A, Wolf F, Volgushev M. Fast computations in cortical ensembles require rapid initiation of action potentials. J Neurosci. 2013;33:2281–92.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nikitin ES, Bal NV, Malyshev A, Ierusalimsky VN, Spivak Y, Balaban PM, et al. Encoding of High Frequencies Improves with Maturation of Action Potential Generation in Cultured Neocortical Neurons. Front Cell Neurosci. 2017;11:28.

Article  PubMed  PubMed Central  Google Scholar 

Ierusalimsky VN, Balaban PM, Nikitin ES. Nav1.6 but not KCa3.1 channels contribute to heterogeneity in coding abilities and dynamics of action potentials in the L5 neocortical pyramidal neurons. Biochem Biophys Res Commun. 2022;615:102–8.

Article  CAS  PubMed  Google Scholar 

Destexhe A, Rudolph M, Pare D. The high-conductance state of neocortical neurons in vivo. Nat Rev Neurosci. 2003;4:739–51.

Article  CAS  PubMed 

Comments (0)

No login
gif