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Modulation of Kv7 channels and excitability in the brain

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Abstract

Neuronal Kv7 channels underlie a voltage-gated non-inactivating potassium current known as the M-current. Due to its particular characteristics, Kv7 channels show pronounced control over the excitability of neurons. We will discuss various factors that have been shown to drastically alter the activity of this channel such as protein and phospholipid interactions, phosphorylation, calcium, and numerous neurotransmitters. Kv7 channels locate to key areas for the control of action potential initiation and propagation. Moreover, we will explore the dynamic surface expression of the channel modulated by neurotransmitters and neural activity. We will also focus on known principle functions of neural Kv7 channels: control of resting membrane potential and spiking threshold, setting the firing frequency, afterhyperpolarization after burst firing, theta resonance, and transient hyperexcitability from neurotransmitter-induced suppression of the M-current. Finally, we will discuss the contribution of altered Kv7 activity to pathologies such as epilepsy and cognitive deficits.

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Abbreviations

PKC:

Protein kinase C

PP1:

Protein phosphatase 1

PP2A:

Protein phosphatase 2A

AKAP:

A-kinase anchoring protein

PLC:

Phospholipace C

DAG:

Diacylglycerol

IP3:

Inositol triphosphate

PIP2:

Phosphatidylinositol 4,5-bis phosphate

CaM:

Calmodulin

RMP:

Resting membrane potential

AIS:

Axon initial segment

GSK3β:

Glycogen synthase kinase 3β

CRMP-2:

Collapsin response mediator protein 2

Nav:

Voltage-gated sodium chanel

AHP:

Afterhyperpolarization

SNARE:

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor

EPSPs:

Excitatory post-synaptic potentials

ROS:

Reactive oxygen species

BFNC:

Benign familial neonatal convulsions

References

  1. Jentsch TJ (2000) Neuronal KCNQ potassium channels: physiology and role in disease. Nat Rev Neurosci 1(1):21–30. doi:10.1038/35036198

    Article  CAS  PubMed  Google Scholar 

  2. Delmas P, Brown DA (2005) Pathways modulating neural KCNQ/M (Kv7) potassium channels. Nat Rev Neurosci 6(11):850–862. doi:10.1038/nrn1785

    Article  CAS  PubMed  Google Scholar 

  3. Miceli F, Cilio MR, Taglialatela M, Bezanilla F (2009) Gating currents from neuronal K(V)7.4 channels: general features and correlation with the ionic conductance. Channels (Austin) 3(4):274–283

    Article  Google Scholar 

  4. Battefeld A, Tran BT, Gavrilis J, Cooper EC, Kole MH (2014) Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons. J Neurosci 34(10):3719–3732. doi:10.1523/JNEUROSCI.4206-13.2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Halliwell JV, Adams PR (1982) Voltage-clamp analysis of muscarinic excitation in hippocampal neurons. Brain Res 250(1):71–92

    Article  CAS  PubMed  Google Scholar 

  6. Robbins J (2001) KCNQ potassium channels: physiology, pathophysiology, and pharmacology. Pharmacol Ther 90(1):1–19

    Article  CAS  PubMed  Google Scholar 

  7. Wang HS, Pan Z, Shi W, Brown BS, Wymore RS, Cohen IS, Dixon JE, McKinnon D (1998) KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science 282(5395):1890–1893

    Article  CAS  PubMed  Google Scholar 

  8. Cooper EC, Aldape KD, Abosch A, Barbaro NM, Berger MS, Peacock WS, Jan YN, Jan LY (2000) Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy. Proc Natl Acad Sci USA 97(9):4914–4919. doi:10.1073/pnas.090092797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Adams PR, Brown DA (1980) Luteinizing hormone-releasing factor and muscarinic agonists act on the same voltage-sensitive K+-current in bullfrog sympathetic neurones. Br J Pharmacol 68(3):353–355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tatulian L, Delmas P, Abogadie FC, Brown DA (2001) Activation of expressed KCNQ potassium currents and native neuronal M-type potassium currents by the anti-convulsant drug retigabine. J Neurosci 21(15):5535–5545

    CAS  PubMed  Google Scholar 

  11. Adelman JP, Maylie J, Sah P (2012) Small-conductance Ca2+-activated K+ channels: form and function. Annu Rev Physiol 74:245–269. doi:10.1146/annurev-physiol-020911-153336

    Article  CAS  PubMed  Google Scholar 

  12. Shapiro MS, Roche JP, Kaftan EJ, Cruzblanca H, Mackie K, Hille B (2000) Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3K(+) channels that underlie the neuronal M current. J Neurosci 20(5):1710–1721

    CAS  PubMed  Google Scholar 

  13. Adams PR, Brown DA, Constanti A (1982) Pharmacological inhibition of the M-current. J Physiol 332:223–262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Cook L, Nickolson VJ, Steinfels GF, Rohrbach KW, Denoble VJ (1990) Cognition enhancement by the acetylcholine releaser DuP 996. Drug Dev Res 19(3):301–314. doi:10.1002/ddr.430190308

    Article  CAS  Google Scholar 

  15. Sanguinetti MC, Curran ME, Zou A, Shen J, Spector PS, Atkinson DL, Keating MT (1996) Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel. Nature 384(6604):80–83. doi:10.1038/384080a0

    Article  CAS  PubMed  Google Scholar 

  16. Nakajo K, Ulbrich MH, Kubo Y, Isacoff EY (2010) Stoichiometry of the KCNQ1–KCNE1 ion channel complex. Proc Natl Acad Sci USA 107(44):18862–18867. doi:10.1073/pnas.1010354107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Neyroud N, Tesson F, Denjoy I, Leibovici M, Donger C, Barhanin J, Faure S, Gary F, Coumel P, Petit C, Schwartz K, Guicheney P (1997) A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. Nat Genet 15(2):186–189. doi:10.1038/ng0297-186

    Article  CAS  PubMed  Google Scholar 

  18. Ng FL, Davis AJ, Jepps TA, Harhun MI, Yeung SY, Wan A, Reddy M, Melville D, Nardi A, Khong TK, Greenwood IA (2011) Expression and function of the K(+) channel KCNQ genes in human arteries. Br J Pharmacol 162(1):42–53. doi:10.1111/j.1476-5381.2010.01027.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Schroeder BC, Kubisch C, Stein V, Jentsch TJ (1998) Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy. Nature 396(6712):687–690. doi:10.1038/25367

    Article  CAS  PubMed  Google Scholar 

  20. Kole MH, Cooper EC (2014) Axonal Kv7.2/7.3 channels: caught in the act. Channels (Austin) 8(4):288–289. doi:10.4161/chan.29965

    Article  Google Scholar 

  21. Soh H, Pant R, LoTurco JJ, Tzingounis AV (2014) Conditional deletions of epilepsy-associated KCNQ2 and KCNQ3 channels from cerebral cortex cause differential effects on neuronal excitability. J Neurosci 34(15):5311–5321. doi:10.1523/JNEUROSCI.3919-13.2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Marcotti W, Johnson SL, Holley MC, Kros CJ (2003) Developmental changes in the expression of potassium currents of embryonic, neonatal and mature mouse inner hair cells. J Physiol 548(Pt 2):383–400. doi:10.1113/jphysiol.2002.034801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kharkovets T, Hardelin JP, Safieddine S, Schweizer M, El-Amraoui A, Petit C, Jentsch TJ (2000) KCNQ4, a K+ channel mutated in a form of dominant deafness, is expressed in the inner ear and the central auditory pathway. Proc Natl Acad Sci USA 97(8):4333–4338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kharkovets T, Dedek K, Maier H, Schweizer M, Khimich D, Nouvian R, Vardanyan V, Leuwer R, Moser T, Jentsch TJ (2006) Mice with altered KCNQ4 K+ channels implicate sensory outer hair cells in human progressive deafness. EMBO J 25(3):642–652. doi:10.1038/sj.emboj.7600951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Brueggemann LI, Mackie AR, Cribbs LL, Freda J, Tripathi A, Majetschak M, Byron KL (2014) Differential protein kinase C-dependent modulation of Kv7.4 and Kv7.5 subunits of vascular Kv7 channels. J Biol Chem 289(4):2099–2111. doi:10.1074/jbc.M113.527820

    Article  CAS  PubMed  Google Scholar 

  26. Ohya S, Asakura K, Muraki K, Watanabe M, Imaizumi Y (2002) Molecular and functional characterization of ERG, KCNQ, and KCNE subtypes in rat stomach smooth muscle. Am J Physiol Gastrointest Liver Physiol 282(2):G277–G287. doi:10.1152/ajpgi.00200.2001

    Article  CAS  PubMed  Google Scholar 

  27. Greenwood IA, Ohya S (2009) New tricks for old dogs: KCNQ expression and role in smooth muscle. Br J Pharmacol 156(8):1196–1203. doi:10.1111/j.1476-5381.2009.00131.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hoshi N, Zhang JS, Omaki M, Takeuchi T, Yokoyama S, Wanaverbecq N, Langeberg LK, Yoneda Y, Scott JD, Brown DA, Higashida H (2003) AKAP150 signaling complex promotes suppression of the M-current by muscarinic agonists. Nat Neurosci 6(6):564–571. doi:10.1038/nn1062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Suh BC, Hille B (2008) PIP2 is a necessary cofactor for ion channel function: how and why? Annu Rev Biophys 37:175–195. doi:10.1146/annurev.biophys.37.032807.125859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Suh BC, Inoue T, Meyer T, Hille B (2006) Rapid chemically induced changes of PtdIns(4,5)P2 gate KCNQ ion channels. Science 314(5804):1454–1457. doi:10.1126/science.1131163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. McLaughlin S, Wang J, Gambhir A, Murray D (2002) PIP(2) and proteins: interactions, organization, and information flow. Annu Rev Biophys Biomol Struct 31:151–175. doi:10.1146/annurev.biophys.31.082901.134259

    Article  CAS  PubMed  Google Scholar 

  32. Rusten TE, Stenmark H (2006) Analyzing phosphoinositides and their interacting proteins. Nat Methods 3(4):251–258. doi:10.1038/nmeth867

    Article  CAS  PubMed  Google Scholar 

  33. Li Y, Zaydman MA, Wu D, Shi J, Guan M, Virgin-Downey B, Cui J (2011) KCNE1 enhances phosphatidylinositol 4,5-bisphosphate (PIP2) sensitivity of IKs to modulate channel activity. Proc Natl Acad Sci USA 108(22):9095–9100. doi:10.1073/pnas.1100872108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Zhang W, Linden DJ (2003) The other side of the engram: experience-driven changes in neuronal intrinsic excitability. Nat Rev Neurosci 4(11):885–900. doi:10.1038/nrn1248

    Article  CAS  PubMed  Google Scholar 

  35. Li Y, Gamper N, Hilgemann DW, Shapiro MS (2005) Regulation of Kv7 (KCNQ) K+ channel open probability by phosphatidylinositol 4,5-bisphosphate. J Neurosci 25(43):9825–9835. doi:10.1523/jneurosci.2597-05.2005

    Article  CAS  PubMed  Google Scholar 

  36. Eckey K, Wrobel E, Strutz-Seebohm N, Pott L, Schmitt N, Seebohm G (2014) Novel Kv7.1-phosphatidylinositol 4,5-bisphosphate interaction sites uncovered by charge neutralization scanning. J Biol Chem 289(33):22749–22758. doi:10.1074/jbc.M114.589796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zaydman MA, Silva JR, Delaloye K, Li Y, Liang H, Larsson HP, Shi J, Cui J (2013) Kv7.1 ion channels require a lipid to couple voltage sensing to pore opening. Proc Natl Acad Sci USA 110(32):13180–13185. doi:10.1073/pnas.1305167110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Zhang L, Ouyang M, Ganellin CR, Thomas SA (2013) The slow afterhyperpolarization: a target of beta1-adrenergic signaling in hippocampus-dependent memory retrieval. J Neurosci 33(11):5006–5016. doi:10.1523/jneurosci.3834-12.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Zaydman MA, Cui J (2014) PIP2 regulation of KCNQ channels: biophysical and molecular mechanisms for lipid modulation of voltage-dependent gating. Front Physiol 5:195. doi:10.3389/fphys.2014.00195

    Article  PubMed  PubMed Central  Google Scholar 

  40. Kim KS, Duignan KM, Hawryluk JM, Soh H, Tzingounis AV (2016) The voltage activation of cortical KCNQ channels depends on global PIP2 levels. Biophys J 110(5):1089–1098. doi:10.1016/j.bpj.2016.01.006

    Article  CAS  PubMed  Google Scholar 

  41. Suh BC, Horowitz LF, Hirdes W, Mackie K, Hille B (2004) Regulation of KCNQ2/KCNQ3 current by G protein cycling: the kinetics of receptor-mediated signaling by Gq. J Gen Physiol 123(6):663–683. doi:10.1085/jgp.200409029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Haitin Y, Attali B (2008) The C-terminus of Kv7 channels: a multifunctional module. J Physiol 586(Pt 7):1803–1810. doi:10.1113/jphysiol.2007.149187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kang S, Xu M, Cooper EC, Hoshi N (2014) Channel-anchored protein kinase CK2 and protein phosphatase 1 reciprocally regulate KCNQ2-containing M-channels via phosphorylation of calmodulin. J Biol Chem 289(16):11536–11544. doi:10.1074/jbc.M113.528497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kosenko A, Kang S, Smith IM, Greene DL, Langeberg LK, Scott JD, Hoshi N (2012) Coordinated signal integration at the M-type potassium channel upon muscarinic stimulation. EMBO J 31(14):3147–3156. doi:10.1038/emboj.2012.156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hughes S, Marsh SJ, Tinker A, Brown DA (2007) PIP2-dependent inhibition of M-type (Kv7. 2/7.3) potassium channels: direct on-line assessment of PIP2 depletion by Gq-coupled receptors in single living neurons. Pflügers Arch Eur J Physiol 455(1):115–124

    Article  CAS  Google Scholar 

  46. Hoshi N, Langeberg LK, Scott JD (2005) Distinct enzyme combinations in AKAP signalling complexes permit functional diversity. Nat Cell Biol 7(11):1066–1073. doi:10.1038/ncb1315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Wong W, Scott JD (2004) AKAP signalling complexes: focal points in space and time. Nat Rev Mol Cell Biol 5(12):959–970. doi:10.1038/nrm1527

    Article  CAS  PubMed  Google Scholar 

  48. Delint-Ramirez I, Willoughby D, Hammond GR, Ayling LJ, Cooper DM (2011) Palmitoylation targets AKAP79 protein to lipid rafts and promotes its regulation of calcium-sensitive adenylyl cyclase type 8. J Biol Chem 286(38):32962–32975. doi:10.1074/jbc.M111.243899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Etxeberria A, Aivar P, Rodriguez-Alfaro JA, Alaimo A, Villace P, Gomez-Posada JC, Areso P, Villarroel A (2008) Calmodulin regulates the trafficking of KCNQ2 potassium channels. FASEB J 22(4):1135–1143. doi:10.1096/fj.07-9712com

    Article  CAS  PubMed  Google Scholar 

  50. Alaimo A, Gomez-Posada JC, Aivar P, Etxeberria A, Rodriguez-Alfaro JA, Areso P, Villarroel A (2009) Calmodulin activation limits the rate of KCNQ2 K+ channel exit from the endoplasmic reticulum. J Biol Chem 284(31):20668–20675. doi:10.1074/jbc.M109.019539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Alberdi A, Gomis-Perez C, Bernardo-Seisdedos G, Alaimo A, Malo C, Aldaregia J, Lopez-Robles C, Areso P, Butz E, Wahl-Schott C, Villarroel A (2015) Uncoupling PIP2-calmodulin regulation of Kv7.2 channels by an assembly destabilizing epileptogenic mutation. J Cell Sci 128(21):4014–4023. doi:10.1242/jcs.176420

    Article  CAS  PubMed  Google Scholar 

  52. Levitan IB (2006) Signaling protein complexes associated with neuronal ion channels. Nat Neurosci 9(3):305–310. doi:10.1038/nn1647

    Article  CAS  PubMed  Google Scholar 

  53. Kosenko A, Hoshi N (2013) A change in configuration of the calmodulin-KCNQ channel complex underlies Ca2+-dependent modulation of KCNQ channel activity. PLoS One 8(12):e82290. doi:10.1371/journal.pone.0082290

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Sachyani D, Dvir M, Strulovich R, Tria G, Tobelaim W, Peretz A, Pongs O, Svergun D, Attali B, Hirsch JA (2014) Structural basis of a Kv7.1 potassium channel gating module: studies of the intracellular c-terminal domain in complex with calmodulin. Structure 22(11):1582–1594. doi:10.1016/j.str.2014.07.016

    Article  CAS  PubMed  Google Scholar 

  55. Alaimo A, Alberdi A, Gomis-Perez C, Fernandez-Orth J, Gomez-Posada JC, Areso P, Villarroel A (2013) Cooperativity between calmodulin-binding sites in Kv7.2 channels. J Cell Sci 126(Pt 1):244–253. doi:10.1242/jcs.114082

    Article  CAS  PubMed  Google Scholar 

  56. Alaimo A, Alberdi A, Gomis-Perez C, Fernandez-Orth J, Bernardo-Seisdedos G, Malo C, Millet O, Areso P, Villarroel A (2014) Pivoting between calmodulin lobes triggered by calcium in the Kv7.2/calmodulin complex. PLoS One 9(1):e86711. doi:10.1371/journal.pone.0086711

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Devaux JJ, Kleopa KA, Cooper EC, Scherer SS (2004) KCNQ2 is a nodal K+ channel. J Neurosci 24(5):1236–1244. doi:10.1523/JNEUROSCI.4512-03.2004

    Article  CAS  PubMed  Google Scholar 

  58. Pan Z, Kao T, Horvath Z, Lemos J, Sul JY, Cranstoun SD, Bennett V, Scherer SS, Cooper EC (2006) A common ankyrin-G-based mechanism retains KCNQ and NaV channels at electrically active domains of the axon. J Neurosci 26(10):2599–2613. doi:10.1523/jneurosci.4314-05.2006

    Article  CAS  PubMed  Google Scholar 

  59. Regev N, Degani-Katzav N, Korngreen A, Etzioni A, Siloni S, Alaimo A, Chikvashvili D, Villarroel A, Attali B, Lotan I (2009) Selective interaction of syntaxin 1A with KCNQ2: possible implications for specific modulation of presynaptic activity. PLoS One 4(8):e6586. doi:10.1371/journal.pone.0006586

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Etzioni A, Siloni S, Chikvashvilli D, Strulovich R, Sachyani D, Regev N, Greitzer-Antes D, Hirsch JA, Lotan I (2011) Regulation of neuronal M-channel gating in an isoform-specific manner: functional interplay between calmodulin and syntaxin 1A. J Neurosci 31(40):14158–14171. doi:10.1523/jneurosci.2666-11.2011

    Article  CAS  PubMed  Google Scholar 

  61. Brackenbury WJ, Isom LL (2011) Na channel beta subunits: overachievers of the ion channel family. Front Pharmacol 2:53. doi:10.3389/fphar.2011.00053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Marionneau C, Carrasquillo Y, Norris AJ, Townsend RR, Isom LL, Link AJ, Nerbonne JM (2012) The sodium channel accessory subunit Navbeta1 regulates neuronal excitability through modulation of repolarizing voltage-gated K(+) channels. J Neurosci 32(17):5716–5727. doi:10.1523/jneurosci.6450-11.2012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Nguyen HM, Miyazaki H, Hoshi N, Smith BJ, Nukina N, Goldin AL, Chandy KG (2012) Modulation of voltage-gated K+ channels by the sodium channel beta1 subunit. Proc Natl Acad Sci USA 109(45):18577–18582. doi:10.1073/pnas.1209142109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Luo Y, Bolon B, Kahn S, Bennett BD, Babu-Khan S, Denis P, Fan W, Kha H, Zhang J, Gong Y, Martin L, Louis JC, Yan Q, Richards WG, Citron M, Vassar R (2001) Mice deficient in BACE1, the Alzheimer’s beta-secretase, have normal phenotype and abolished beta-amyloid generation. Nat Neurosci 4(3):231–232. doi:10.1038/85059

    Article  CAS  PubMed  Google Scholar 

  65. Wong HK, Sakurai T, Oyama F, Kaneko K, Wada K, Miyazaki H, Kurosawa M, De Strooper B, Saftig P, Nukina N (2005) beta Subunits of voltage-gated sodium channels are novel substrates of beta-site amyloid precursor protein-cleaving enzyme (BACE1) and gamma-secretase. J Biol Chem 280(24):23009–23017. doi:10.1074/jbc.M414648200

    Article  CAS  PubMed  Google Scholar 

  66. Hessler S, Zheng F, Hartmann S, Rittger A, Lehnert S, Volkel M, Nissen M, Edelmann E, Saftig P, Schwake M, Huth T, Alzheimer C (2015) beta-Secretase BACE1 regulates hippocampal and reconstituted M-currents in a beta-subunit-like fashion. J Neurosci 35(8):3298–3311. doi:10.1523/JNEUROSCI.3127-14.2015

    Article  CAS  PubMed  Google Scholar 

  67. Jiang L, Kosenko A, Yu C, Huang L, Li X, Hoshi N (2015) Activation of m1 muscarinic acetylcholine receptor induces surface transport of KCNQ channels through a CRMP-2-mediated pathway. J Cell Sci 128(22):4235–4245. doi:10.1242/jcs.175547

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Brown D (1988) M-currents: an update. Trends Neurosci 11(7):294–299

    Article  CAS  PubMed  Google Scholar 

  69. Marrion NV (1997) Control of M-current. Annu Rev Physiol 59:483–504. doi:10.1146/annurev.physiol.59.1.483

    Article  CAS  PubMed  Google Scholar 

  70. Zaika O, Lara LS, Gamper N, Hilgemann DW, Jaffe DB, Shapiro MS (2006) Angiotensin II regulates neuronal excitability via phosphatidylinositol 4,5-bisphosphate-dependent modulation of Kv7 (M-type) K+ channels. J Physiol 575(Pt 1):49–67. doi:10.1113/jphysiol.2006.114074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Jones SW (1985) Muscarinic and peptidergic excitation of bull-frog sympathetic neurones. J Physiol 366:63–87

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Colino A, Halliwell JV (1987) Differential modulation of three separate K-conductances in hippocampal CA1 neurons by serotonin. Nature 328(6125):73–77. doi:10.1038/328073a0

    Article  CAS  PubMed  Google Scholar 

  73. Marrion NV, Smart TG, Marsh SJ, Brown DA (1989) Muscarinic suppression of the M-current in the rat sympathetic ganglion is mediated by receptors of the M1-subtype. Br J Pharmacol 98(2):557–573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Bernheim L, Mathie A, Hille B (1992) Characterization of muscarinic receptor subtypes inhibiting Ca2+ current and M current in rat sympathetic neurons. Proc Natl Acad Sci USA 89(20):9544–9548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Charpak S, Gahwiler BH, Do KQ, Knopfel T (1990) Potassium conductances in hippocampal neurons blocked by excitatory amino-acid transmitters. Nature 347(6295):765–767. doi:10.1038/347765a0

    Article  CAS  PubMed  Google Scholar 

  76. Moore SD, Madamba SG, Schweitzer P, Siggins GR (1994) Voltage-dependent effects of opioid peptides on hippocampal CA3 pyramidal neurons in vitro. J Neurosci 14(2):809–820

    CAS  PubMed  Google Scholar 

  77. Constanti A, Brown DA (1981) M-currents in voltage-clamped mammalian sympathetic neurones. Neurosci Lett 24(3):289–294

    Article  CAS  PubMed  Google Scholar 

  78. Shapiro MS, Wollmuth LP, Hille B (1994) Angiotensin II inhibits calcium and M current channels in rat sympathetic neurons via G proteins. Neuron 12(6):1319–1329

    Article  CAS  PubMed  Google Scholar 

  79. Brown DA, Adams PR (1980) Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone. Nature 283(5748):673–676

    Article  CAS  PubMed  Google Scholar 

  80. Storm JF (1990) Potassium currents in hippocampal pyramidal cells. Prog Brain Res 83:161–187

    Article  CAS  PubMed  Google Scholar 

  81. Suh BC, Hille B (2002) Recovery from muscarinic modulation of M current channels requires phosphatidylinositol 4,5-bisphosphate synthesis. Neuron 35(3):507–520

    Article  CAS  PubMed  Google Scholar 

  82. Zhang H, Craciun LC, Mirshahi T, Rohacs T, Lopes CM, Jin T, Logothetis DE (2003) PIP(2) activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents. Neuron 37(6):963–975

    Article  CAS  PubMed  Google Scholar 

  83. Winks JS, Hughes S, Filippov AK, Tatulian L, Abogadie FC, Brown DA, Marsh SJ (2005) Relationship between membrane phosphatidylinositol-4,5-bisphosphate and receptor-mediated inhibition of native neuronal M channels. J Neurosci 25(13):3400–3413. doi:10.1523/jneurosci.3231-04.2005

    Article  CAS  PubMed  Google Scholar 

  84. Higashida H, Brown DA (1986) Two polyphosphatidylinositide metabolites control two K+ currents in a neuronal cell. Nature 323(6086):333–335. doi:10.1038/323333a0

    Article  CAS  PubMed  Google Scholar 

  85. Bosma MM, Hille B (1989) Protein kinase C is not necessary for peptide-induced suppression of M current or for desensitization of the peptide receptors. Proc Natl Acad Sci USA 86(8):2943–2947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Hoshi N, Langeberg LK, Gould CM, Newton AC, Scott JD (2010) Interaction with AKAP79 modifies the cellular pharmacology of PKC. Mol Cell 37(4):541–550. doi:10.1016/j.molcel.2010.01.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Smith IM, Hoshi N (2011) ATP competitive protein kinase C inhibitors demonstrate distinct state-dependent inhibition. PLoS One 6(10):e26338. doi:10.1371/journal.pone.0026338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Tunquist BJ, Hoshi N, Guire ES, Zhang F, Mullendorff K, Langeberg LK, Raber J, Scott JD (2008) Loss of AKAP150 perturbs distinct neuronal processes in mice. Proc Natl Acad Sci USA 105(34):12557–12562. doi:10.1073/pnas.0805922105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Kirkwood A, Lisman JE (1992) Action potentials produce a long-term enhancement of M-current in frog sympathetic ganglion. Brain Res 580(1–2):281–287

    Article  CAS  PubMed  Google Scholar 

  90. Gamper N, Shapiro MS (2003) Calmodulin mediates Ca2+-dependent modulation of M-type K+ channels. J Gen Physiol 122(1):17–31. doi:10.1085/jgp.200208783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Bal M, Zhang J, Hernandez CC, Zaika O, Shapiro MS (2010) Ca2+/calmodulin disrupts AKAP79/150 interactions with KCNQ (M-Type) K+ channels. J Neurosci 30(6):2311–2323. doi:10.1523/JNEUROSCI.5175-09.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Sihn CR, Kim HJ, Woltz RL, Yarov-Yarovoy V, Yang PC, Xu J, Clancy CE, Zhang XD, Chiamvimonvat N, Yamoah EN (2016) Mechanisms of Calmodulin Regulation of Different Isoforms of Kv7.4 K+ Channels. J Biol Chem 291(5):2499–2509. doi:10.1074/jbc.M115.668236

    Article  CAS  PubMed  Google Scholar 

  93. Brown DA, Passmore GM (2009) Neural KCNQ (Kv7) channels. Br J Pharmacol 156(8):1185–1195. doi:10.1111/j.1476-5381.2009.00111.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Koyama S, Appel SB (2006) Characterization of M-current in ventral tegmental area dopamine neurons. J Neurophysiol 96(2):535–543. doi:10.1152/jn.00574.2005

    Article  CAS  PubMed  Google Scholar 

  95. Wladyka CL, Kunze DL (2006) KCNQ/M-currents contribute to the resting membrane potential in rat visceral sensory neurons. J Physiol 575(Pt 1):175–189. doi:10.1113/jphysiol.2006.113308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Guan D, Higgs MH, Horton LR, Spain WJ, Foehring RC (2011) Contributions of Kv7-mediated potassium current to sub- and suprathreshold responses of rat layer II/III neocortical pyramidal neurons. J Neurophysiol 106(4):1722–1733. doi:10.1152/jn.00211.2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Huang H, Trussell LO (2011) KCNQ5 channels control resting properties and release probability of a synapse. Nat Neurosci 14(7):840–847. doi:10.1038/nn.2830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Schwarz JR, Glassmeier G, Cooper EC, Kao TC, Nodera H, Tabuena D, Kaji R, Bostock H (2006) KCNQ channels mediate IKs, a slow K+ current regulating excitability in the rat node of Ranvier. J Physiol 573(Pt 1):17–34. doi:10.1113/jphysiol.2006.106815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Martire M, Castaldo P, D’Amico M, Preziosi P, Annunziato L, Taglialatela M (2004) M channels containing KCNQ2 subunits modulate norepinephrine, aspartate, and GABA release from hippocampal nerve terminals. J Neurosci 24(3):592–597. doi:10.1523/JNEUROSCI.3143-03.2004

    Article  CAS  PubMed  Google Scholar 

  100. Vervaeke K, Gu N, Agdestein C, Hu H, Storm JF (2006) Kv7/KCNQ/M-channels in rat glutamatergic hippocampal axons and their role in regulation of excitability and transmitter release. J Physiol 576(Pt 1):235–256. doi:10.1113/jphysiol.2006.111336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Shah MM, Migliore M, Valencia I, Cooper EC, Brown DA (2008) Functional significance of axonal Kv7 channels in hippocampal pyramidal neurons. Proc Natl Acad Sci USA 105(22):7869–7874. doi:10.1073/pnas.0802805105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Shah MM, Migliore M, Brown DA (2011) Differential effects of Kv7 (M-) channels on synaptic integration in distinct subcellular compartments of rat hippocampal pyramidal neurons. J Physiol 589(Pt 24):6029–6038. doi:10.1113/jphysiol.2011.220913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Storm JF (1989) An after-hyperpolarization of medium duration in rat hippocampal pyramidal cells. J Physiol 409:171–190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Gu N, Vervaeke K, Hu H, Storm JF (2005) Kv7/KCNQ/M and HCN/h, but not KCa2/SK channels, contribute to the somatic medium after-hyperpolarization and excitability control in CA1 hippocampal pyramidal cells. J Physiol 566(Pt 3):689–715. doi:10.1113/jphysiol.2005.086835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Stocker M, Krause M, Pedarzani P (1999) An apamin-sensitive Ca2+-activated K+ current in hippocampal pyramidal neurons. Proc Natl Acad Sci USA 96(8):4662–4667

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Mateos-Aparicio P, Murphy R, Storm JF (2014) Complementary functions of SK and Kv7/M potassium channels in excitability control and synaptic integration in rat hippocampal dentate granule cells. J Physiol 592(4):669–693. doi:10.1113/jphysiol.2013.267872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Sanchez G, Rodriguez MJ, Pomata P, Rela L, Murer MG (2011) Reduction of an afterhyperpolarization current increases excitability in striatal cholinergic interneurons in rat parkinsonism. J Neurosci 31(17):6553–6564. doi:10.1523/jneurosci.6345-10.2011

    Article  CAS  PubMed  Google Scholar 

  108. Tzingounis AV, Kobayashi M, Takamatsu K, Nicoll RA (2007) Hippocalcin gates the calcium activation of the slow afterhyperpolarization in hippocampal pyramidal cells. Neuron 53(4):487–493. doi:10.1016/j.neuron.2007.01.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Andrade R, Foehring RC, Tzingounis AV (2012) The calcium-activated slow AHP: cutting through the Gordian knot. Front Cell Neurosci 6:47. doi:10.3389/fncel.2012.00047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Zhang Q, Zhou P, Chen Z, Li M, Jiang H, Gao Z, Yang H (2013) Dynamic PIP2 interactions with voltage sensor elements contribute to KCNQ2 channel gating. Proc Natl Acad Sci USA 110(50):20093–20098. doi:10.1073/pnas.1312483110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Aiken SP, Lampe BJ, Murphy PA, Brown BS (1995) Reduction of spike frequency adaptation and blockade of M-current in rat CA1 pyramidal neurones by linopirdine (DuP 996), a neurotransmitter release enhancer. Br J Pharmacol 115(7):1163–1168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Nigro MJ, Mateos-Aparicio P, Storm JF (2014) Expression and functional roles of Kv7/KCNQ/M-channels in rat medial entorhinal cortex layer II stellate cells. J Neurosci 34(20):6807–6812. doi:10.1523/JNEUROSCI.4153-13.2014

    Article  CAS  PubMed  Google Scholar 

  113. Hawryluk JM, Moreira TS, Takakura AC, Wenker IC, Tzingounis AV, Mulkey DK (2012) KCNQ channels determine serotonergic modulation of ventral surface chemoreceptors and respiratory drive. J Neurosci 32(47):16943–16952. doi:10.1523/jneurosci.3043-12.2012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Lawrence JJ, Saraga F, Churchill JF, Statland JM, Travis KE, Skinner FK, McBain CJ (2006) Somatodendritic Kv7/KCNQ/M channels control interspike interval in hippocampal interneurons. J Neurosci 26(47):12325–12338. doi:10.1523/JNEUROSCI.3521-06.2006

    Article  CAS  PubMed  Google Scholar 

  115. Madison DV, Nicoll RA (1984) Control of the repetitive discharge of rat CA 1 pyramidal neurones in vitro. J Physiol 354:319–331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Hu H, Vervaeke K, Storm JF (2002) Two forms of electrical resonance at theta frequencies, generated by M-current, h-current and persistent Na + current in rat hippocampal pyramidal cells. J Physiol 545(Pt 3):783–805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Ge L, Liu XD (2016) Electrical resonance with voltage-gated ion channels: perspectives from biophysical mechanisms and neural electrophysiology. Acta Pharmacol Sin 37(1):67–74. doi:10.1038/aps.2015.140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Winson J (1978) Loss of hippocampal theta rhythm results in spatial memory deficit in the rat. Science 201(4351):160–163

    Article  CAS  PubMed  Google Scholar 

  119. Huerta PT, Lisman JE (1993) Heightened synaptic plasticity of hippocampal CA1 neurons during a cholinergically induced rhythmic state. Nature 364(6439):723–725. doi:10.1038/364723a0

    Article  CAS  PubMed  Google Scholar 

  120. Buzsaki G (2002) Theta oscillations in the hippocampus. Neuron 33(3):325–340

    Article  CAS  PubMed  Google Scholar 

  121. Bland BH (1986) The physiology and pharmacology of hippocampal formation theta rhythms. Prog Neurobiol 26(1):1–54

    Article  CAS  PubMed  Google Scholar 

  122. Sarnthein J, Petsche H, Rappelsberger P, Shaw GL, von Stein A (1998) Synchronization between prefrontal and posterior association cortex during human working memory. Proc Natl Acad Sci USA 95(12):7092–7096

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Olvera-Cortes E, Guevara MA, Gonzalez-Burgos I (2004) Increase of the hippocampal theta activity in the Morris water maze reflects learning rather than motor activity. Brain Res Bull 62(5):379–384. doi:10.1016/j.brainresbull.2003.10.003

    Article  PubMed  Google Scholar 

  124. Peters HC, Hu H, Pongs O, Storm JF, Isbrandt D (2005) Conditional transgenic suppression of M channels in mouse brain reveals functions in neuronal excitability, resonance and behavior. Nat Neurosci 8(1):51–60. doi:10.1038/nn1375

    Article  CAS  PubMed  Google Scholar 

  125. Yue C, Yaari Y (2004) KCNQ/M channels control spike afterdepolarization and burst generation in hippocampal neurons. J Neurosci 24(19):4614–4624. doi:10.1523/JNEUROSCI.0765-04.2004

    Article  CAS  PubMed  Google Scholar 

  126. Martinello K, Huang Z, Lujan R, Tran B, Watanabe M, Cooper EC, Brown DA, Shah MM (2015) Cholinergic afferent stimulation induces axonal function plasticity in adult hippocampal granule cells. Neuron 85(2):346–363. doi:10.1016/j.neuron.2014.12.030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Young MB, Thomas SA (2014) M1-muscarinic receptors promote fear memory consolidation via phospholipase C and the M-current. J Neurosci 34(5):1570–1578. doi:10.1523/JNEUROSCI.1040-13.2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Frick A, Magee J, Johnston D (2004) LTP is accompanied by an enhanced local excitability of pyramidal neuron dendrites. Nat Neurosci 7(2):126–135. doi:10.1038/nn1178

    Article  CAS  PubMed  Google Scholar 

  129. Moore SD, Madamba SG, Joels M, Siggins GR (1988) Somatostatin augments the M-current in hippocampal neurons. Science 239(4837):278–280

    Article  CAS  PubMed  Google Scholar 

  130. de Lecea L, Criado JR, Prospero-Garcia O, Gautvik KM, Schweitzer P, Danielson PE, Dunlop CL, Siggins GR, Henriksen SJ, Sutcliffe JG (1996) A cortical neuropeptide with neuronal depressant and sleep-modulating properties. Nature 381(6579):242–245. doi:10.1038/381242a0

    Article  PubMed  Google Scholar 

  131. Madamba SG, Schweitzer P, Siggins GR (1999) Dynorphin selectively augments the M-current in hippocampal CA1 neurons by an opiate receptor mechanism. J Neurophysiol 82(4):1768–1775

    CAS  PubMed  Google Scholar 

  132. Borsotto M, Cavarec L, Bouillot M, Romey G, Macciardi F, Delaye A, Nasroune M, Bastucci M, Sambucy JL, Luan JJ, Charpagne A, Jouet V, Leger R, Lazdunski M, Cohen D, Chumakov I (2007) PP2A-Bgamma subunit and KCNQ2 K+channels in bipolar disorder. Pharmacogenomics J 7(2):123–132. doi:10.1038/sj.tpj.6500400

    Article  CAS  PubMed  Google Scholar 

  133. Wildburger NC, Laezza F (2012) Control of neuronal ion channel function by glycogen synthase kinase-3: new prospective for an old kinase. Front Mol Neurosci 5:80. doi:10.3389/fnmol.2012.00080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Zhang M, Meng XY, Cui M, Pascal JM, Logothetis DE, Zhang JF (2014) Selective phosphorylation modulates the PIP2 sensitivity of the CaM-SK channel complex. Nat Chem Biol 10(9):753–759. doi:10.1038/nchembio.1592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Gamper N, Zaika O, Li Y, Martin P, Hernandez CC, Perez MR, Wang AY, Jaffe DB, Shapiro MS (2006) Oxidative modification of M-type K(+) channels as a mechanism of cytoprotective neuronal silencing. EMBO J 25(20):4996–5004. doi:10.1038/sj.emboj.7601374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Kim HJ, Jeong MH, Kim KR, Jung CY, Lee SY, Kim H, Koh J, Vuong TA, Jung S, Yang H, Park SK, Choi D, Kim SH, Kang K, Sohn JW, Park JM, Jeon D, Koo SH, Ho WK, Kang JS, Kim ST, Cho H (2016) Protein arginine methylation facilitates KCNQ channel-PIP2 interaction leading to seizure suppression. Elife. doi:10.7554/eLife.17159

    Google Scholar 

  137. Stott JB, Povstyan OV, Carr G, Barrese V, Greenwood IA (2015) G-protein betagamma subunits are positive regulators of Kv7.4 and native vascular Kv7 channel activity. Proc Natl Acad Sci USA 112(20):6497–6502. doi:10.1073/pnas.1418605112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Roper J, Schwarz JR (1989) Heterogeneous distribution of fast and slow potassium channels in myelinated rat nerve fibres. J Physiol 416:93–110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Hamada MS, Kole MH (2015) Myelin loss and axonal ion channel adaptations associated with gray matter neuronal hyperexcitability. J Neurosci 35(18):7272–7286. doi:10.1523/jneurosci.4747-14.2015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Shah M, Mistry M, Marsh SJ, Brown DA, Delmas P (2002) Molecular correlates of the M-current in cultured rat hippocampal neurons. J Physiol 544(Pt 1):29–37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Kapfhamer D, Berger KH, Hopf FW, Seif T, Kharazia V, Bonci A, Heberlein U (2010) Protein Phosphatase 2a and glycogen synthase kinase 3 signaling modulate prepulse inhibition of the acoustic startle response by altering cortical M-Type potassium channel activity. J Neurosci 30(26):8830–8840. doi:10.1523/jneurosci.1292-10.2010

    Article  PubMed  PubMed Central  Google Scholar 

  142. Yue C, Yaari Y (2006) Axo-somatic and apical dendritic Kv7/M channels differentially regulate the intrinsic excitability of adult rat CA1 pyramidal cells. J Neurophysiol 95(6):3480–3495. doi:10.1152/jn.01333.2005

    Article  CAS  PubMed  Google Scholar 

  143. Hu H, Vervaeke K, Storm JF (2007) M-channels (Kv7/KCNQ channels) that regulate synaptic integration, excitability, and spike pattern of CA1 pyramidal cells are located in the perisomatic region. J Neurosci 27(8):1853–1867. doi:10.1523/jneurosci.4463-06.2007

    Article  CAS  PubMed  Google Scholar 

  144. Chen X, Johnston D (2004) Properties of single voltage-dependent K(+) channels in dendrites of CA1 pyramidal neurones of rat hippocampus. J Physiol 559(Pt 1):187–203. doi:10.1113/jphysiol.2004.068114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Sun J, Kapur J (2012) M-type potassium channels modulate Schaffer collateral-CA1 glutamatergic synaptic transmission. J Physiol 590(16):3953–3964. doi:10.1113/jphysiol.2012.235820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Benned-Jensen T, Christensen RK, Denti F, Perrier JF, Rasmussen HB, Olesen SP (2016) Live imaging of Kv7.2/7.3 cell surface dynamics at the axon initial segment: high steady-state stability and calpain-dependent excitotoxic downregulation revealed. J Neurosci 36(7):2261–2266. doi:10.1523/JNEUROSCI.2631-15.2016

    Article  CAS  PubMed  Google Scholar 

  147. Zhang J, Shapiro MS (2012) Activity-dependent transcriptional regulation of M-Type (Kv7) K(+) channels by AKAP79/150-mediated NFAT actions. Neuron 76(6):1133–1146. doi:10.1016/j.neuron.2012.10.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Li C, Lu Q, Huang P, Fu T, Li C, Guo L, Xu X (2015) Activity-dependent downregulation of M-Type (Kv7) K(+) channels surface expression requires the activation of iGluRs/Ca(2)(+)/PKC signaling pathway in hippocampal neuron. Neuropharmacology 95:154–167. doi:10.1016/j.neuropharm.2015.03.004

    Article  CAS  PubMed  Google Scholar 

  149. Kuba H, Yamada R, Ishiguro G, Adachi R (2015) Redistribution of Kv1 and Kv7 enhances neuronal excitability during structural axon initial segment plasticity. Nat Commun 6:8815. doi:10.1038/ncomms9815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Biervert C, Schroeder BC, Kubisch C, Berkovic SF, Propping P, Jentsch TJ, Steinlein OK (1998) A potassium channel mutation in neonatal human epilepsy. Science 279(5349):403–406

    Article  CAS  PubMed  Google Scholar 

  151. Castaldo P, del Giudice EM, Coppola G, Pascotto A, Annunziato L, Taglialatela M (2002) Benign familial neonatal convulsions caused by altered gating of KCNQ2/KCNQ3 potassium channels. J Neurosci 22(2):RC199

    PubMed  Google Scholar 

  152. Abidi A, Devaux JJ, Molinari F, Alcaraz G, Michon FX, Sutera-Sardo J, Becq H, Lacoste C, Altuzarra C, Afenjar A, Mignot C, Doummar D, Isidor B, Guyen SN, Colin E, De La Vaissiere S, Haye D, Trauffler A, Badens C, Prieur F, Lesca G, Villard L, Milh M, Aniksztejn L (2015) A recurrent KCNQ2 pore mutation causing early onset epileptic encephalopathy has a moderate effect on M current but alters subcellular localization of Kv7 channels. Neurobiol Dis 80:80–92. doi:10.1016/j.nbd.2015.04.017

    Article  CAS  PubMed  Google Scholar 

  153. Borgatti R, Zucca C, Cavallini A, Ferrario M, Panzeri C, Castaldo P, Soldovieri MV, Baschirotto C, Bresolin N, Dalla Bernardina B, Taglialatela M, Bassi MT (2004) A novel mutation in KCNQ2 associated with BFNC, drug resistant epilepsy, and mental retardation. Neurology 63(1):57–65

    Article  CAS  PubMed  Google Scholar 

  154. Schwake M, Pusch M, Kharkovets T, Jentsch TJ (2000) Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy. J Biol Chem 275(18):13343–13348

    Article  CAS  PubMed  Google Scholar 

  155. Chung HJ, Jan YN, Jan LY (2006) Polarized axonal surface expression of neuronal KCNQ channels is mediated by multiple signals in the KCNQ2 and KCNQ3 C-terminal domains. Proc Natl Acad Sci USA 103(23):8870–8875. doi:10.1073/pnas.0603376103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Soldovieri MV, Miceli F, Taglialatela M (2011) Driving with no brakes: molecular pathophysiology of Kv7 potassium channels. Physiology (Bethesda) 26(5):365–376. doi:10.1152/physiol.00009.2011

    Article  CAS  Google Scholar 

  157. Dedek K, Fusco L, Teloy N, Steinlein OK (2003) Neonatal convulsions and epileptic encephalopathy in an Italian family with a missense mutation in the fifth transmembrane region of KCNQ2. Epilepsy Res 54(1):21–27

    Article  CAS  PubMed  Google Scholar 

  158. Weckhuysen S, Ivanovic V, Hendrickx R, Van Coster R, Hjalgrim H, Moller RS, Gronborg S, Schoonjans AS, Ceulemans B, Heavin SB, Eltze C, Horvath R, Casara G, Pisano T, Giordano L, Rostasy K, Haberlandt E, Albrecht B, Bevot A, Benkel I, Syrbe S, Sheidley B, Guerrini R, Poduri A, Lemke JR, Mandelstam S, Scheffer I, Angriman M, Striano P, Marini C, Suls A, De Jonghe P (2013) Extending the KCNQ2 encephalopathy spectrum: clinical and neuroimaging findings in 17 patients. Neurology 81(19):1697–1703. doi:10.1212/01.wnl.0000435296.72400.a1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Singh NA, Otto JF, Dahle EJ, Pappas C, Leslie JD, Vilaythong A, Noebels JL, White HS, Wilcox KS, Leppert MF (2008) Mouse models of human KCNQ2 and KCNQ3 mutations for benign familial neonatal convulsions show seizures and neuronal plasticity without synaptic reorganization. J Physiol 586(14):3405–3423. doi:10.1113/jphysiol.2008.154971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Tomonoh Y, Deshimaru M, Araki K, Miyazaki Y, Arasaki T, Tanaka Y, Kitamura H, Mori F, Wakabayashi K, Yamashita S, Saito R, Itoh M, Uchida T, Yamada J, Migita K, Ueno S, Kitaura H, Kakita A, Lossin C, Takano Y, Hirose S (2014) The kick-in system: a novel rapid knock-in strategy. PLoS One 9(2):e88549. doi:10.1371/journal.pone.0088549

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  161. Ihara Y, Tomonoh Y, Deshimaru M, Zhang B, Uchida T, Ishii A, Hirose S (2016) Retigabine, a Kv7.2/Kv7.3-channel opener, attenuates drug-induced seizures in knock-in mice harboring Kcnq2 mutations. PLoS One 11(2):e0150095. doi:10.1371/journal.pone.0150095

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  162. Lothman EW, Bertram EH 3rd, Stringer JL (1991) Functional anatomy of hippocampal seizures. Prog Neurobiol 37(1):1–82

    Article  CAS  PubMed  Google Scholar 

  163. Meriaux C, Franck J, Park DB, Quanico J, Kim YH, Chung CK, Park YM, Steinbusch H, Salzet M, Fournier I (2014) Human temporal lobe epilepsy analyses by tissue proteomics. Hippocampus 24(6):628–642. doi:10.1002/hipo.22246

    Article  CAS  PubMed  Google Scholar 

  164. Weckhuysen S, Mandelstam S, Suls A, Audenaert D, Deconinck T, Claes LR, Deprez L, Smets K, Hristova D, Yordanova I, Jordanova A, Ceulemans B, Jansen A, Hasaerts D, Roelens F, Lagae L, Yendle S, Stanley T, Heron SE, Mulley JC, Berkovic SF, Scheffer IE, de Jonghe P (2012) KCNQ2 encephalopathy: emerging phenotype of a neonatal epileptic encephalopathy. Ann Neurol 71(1):15–25. doi:10.1002/ana.22644

    Article  CAS  PubMed  Google Scholar 

  165. Miceli F, Soldovieri MV, Ambrosino P, De Maria M, Migliore M, Migliore R, Taglialatela M (2015) Early-onset epileptic encephalopathy caused by gain-of-function mutations in the voltage sensor of Kv7.2 and Kv7.3 potassium channel subunits. J Neurosci 35(9):3782–3793. doi:10.1523/JNEUROSCI.4423-14.2015

    Article  CAS  PubMed  Google Scholar 

  166. Devaux J, Abidi A, Roubertie A, Molinari F, Becq H, Lacoste C, Villard L, Milh M, Aniksztejn L (2016) A Kv7.2 mutation associated with early onset epileptic encephalopathy with suppression-burst enhances Kv7/M channel activity. Epilepsia. doi:10.1111/epi.13366

    Google Scholar 

  167. Wickenden AD, Yu W, Zou A, Jegla T, Wagoner PK (2000) Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels. Mol Pharmacol 58(3):591–600

    CAS  PubMed  Google Scholar 

  168. Kay HY, Greene DL, Kang S, Kosenko A, Hoshi N (2015) M-current preservation contributes to anticonvulsant effects of valproic acid. J Clin Invest 125(10):3904–3914. doi:10.1172/JCI79727

    Article  PubMed  PubMed Central  Google Scholar 

  169. Santini E, Porter JT (2010) M-type potassium channels modulate the intrinsic excitability of infralimbic neurons and regulate fear expression and extinction. J Neurosci 30(37):12379–12386. doi:10.1523/jneurosci.1295-10.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Department of Pharmacology, University of California, 360 Med Surge II, Irvine, CA, 92697, USA

    Derek L. Greene & Naoto Hoshi

  2. Department of Physiology and Biophysics, University of California, Irvine, USA

    Naoto Hoshi

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Greene, D.L., Hoshi, N. Modulation of Kv7 channels and excitability in the brain. Cell. Mol. Life Sci. 74, 495–508 (2017). https://doi.org/10.1007/s00018-016-2359-y

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