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PMID: 16777937 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

KCNQ/M-currents contribute to the resting membrane potential in rat visceral sensory neurons.

The Journal of physiology ·Vol. 575 ·No. Pt 1 ·2006-08-15 ·Pages 175-89

Wladyka CL, Kunze DL

Abstract

The M-current is a slowly activating, non-inactivating potassium current that has been shown to be present in numerous cell types. In this study, KCNQ2, Q3 and Q5, the molecular correlates of M-current in neurons, were identified in the visceral sensory neurons of the nodose ganglia from rats through immunocytochemical studies. All neurons showed expression of each of the three proteins. In voltage clamp studies, the cognition-enhancing drug linopirdine (1-50 microM) and its analogue, XE991 (10 microM), quickly and irreversibly blocked a small, slowly activating current that had kinetic properties similar to KCNQ/M-currents. This current activated between -60 and -55 mV, had a voltage-dependent activation time constant of 208 +/- 12 ms at -20 mV, a deactivation time constant of 165 +/- 24 ms at -50 mV and V1/2 of -24 +/- 2 mV, values which are consistent with previous reports for endogenous M-currents. In current clamp studies, these drugs also led to a depolarization of the resting membrane potential at values as negative as -60 mV. Flupirtine (10-20 microM), an M-current activator, caused a 3-14 mV leftward shift in the current-voltage relationship and also led to a hyperpolarization of resting membrane potential. These data indicate that the M-current is present in nodose neurons, is activated at resting membrane potential and that it is physiologically important in regulating excitability by maintaining cells at negative voltages.

MeSH Terms
Aminopyridines/pharmacology Animals Anthracenes/pharmacology Cells, Cultured Dose-Response Relationship, Drug Indoles/pharmacology KCNQ Potassium Channels/analysis,drug effects,metabolism KCNQ2 Potassium Channel/analysis,drug effects,metabolism KCNQ3 Potassium Channel/analysis,drug effects,metabolism Membrane Potentials Neurons, Afferent/chemistry,drug effects,metabolism Nodose Ganglion/chemistry,drug effects,physiology Potassium/metabolism Potassium Channel Blockers/pharmacology Pyridines/pharmacology Rats Rats, Sprague-Dawley Visceral Afferents/chemistry,drug effects,metabolism
Chemicals
10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone Aminopyridines Anthracenes Indoles KCNQ Potassium Channels KCNQ2 Potassium Channel KCNQ3 Potassium Channel Kcnq2 protein, rat Kcnq3 protein, rat Kcnq5 protein, rat Potassium Channel Blockers Pyridines linopirdine flupirtine Potassium
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Wladyka Cynthia L
Rammelkamp Centre for Research and Education R326 MetroHealth Medical Centre, 2500 MetroHealth Drive, Cleveland, OH 44109-1998, USA.
Kunze Diana L
References (50)
50 references, click to expand
  1. Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels.
    Mol Pharmacol. 2000 Sep;58(3):591-600 PMID: 10953053
  2. Ion permeation and block of M-type and delayed rectifier potassium channels. Whole-cell recordings from bullfrog sympathetic neurons.
    J Gen Physiol. 1996 Apr;107(4):473-88 PMID: 8722561
  3. KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel.
    Science. 1998 Dec 4;282(5395):1890-3 PMID: 9836639
  4. Separation of M-like current and ERG current in NG108-15 cells.
    Br J Pharmacol. 1999 Jul;127(5):1213-23 PMID: 10455268
  5. A reduced K+ current due to a novel mutation in KCNQ2 causes neonatal convulsions.
    Ann Neurol. 1999 Sep;46(3):305-12 PMID: 10482260
  6. Two types of K(+) channel subunit, Erg1 and KCNQ2/3, contribute to the M-like current in a mammalian neuronal cell.
    J Neurosci. 1999 Sep 15;19(18):7742-56 PMID: 10479678
  7. De novo KCNQ2 mutations in patients with benign neonatal seizures.
    Neurology. 2004 Dec 14;63(11):2155-8 PMID: 15596769
  8. Conditional transgenic suppression of M channels in mouse brain reveals functions in neuronal excitability, resonance and behavior.
    Nat Neurosci. 2005 Jan;8(1):51-60 PMID: 15608631
  9. Recent developments on KCNQ potassium channel openers.
    Curr Med Chem. 2005;12(4):453-60 PMID: 15720253
  10. 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. 2005 Aug 1;566(Pt 3):689-715 PMID: 15890705
  11. Electrophysiological and functional effects of the KCNQ channel blocker XE991 on murine portal vein smooth muscle cells.
    Br J Pharmacol. 2005 Oct;146(4):585-95 PMID: 16056238
  12. M-type KCNQ2-KCNQ3 potassium channels are modulated by the KCNE2 subunit.
    FEBS Lett. 2000 Sep 1;480(2-3):137-41 PMID: 11034315
  13. Characterization of KCNQ5/Q3 potassium channels expressed in mammalian cells.
    Br J Pharmacol. 2001 Jan;132(2):381-4 PMID: 11159685
  14. Neuronal KCNQ potassium channels: physiology and role in disease.
    Nat Rev Neurosci. 2000 Oct;1(1):21-30 PMID: 11252765
  15. Alternative splicing of KCNQ2 potassium channel transcripts contributes to the functional diversity of M-currents.
    J Physiol. 2001 Mar 1;531(Pt 2):347-58 PMID: 11230508
  16. KCNQ potassium channels: physiology, pathophysiology, and pharmacology.
    Pharmacol Ther. 2001 Apr;90(1):1-19 PMID: 11448722
  17. Activation of expressed KCNQ potassium currents and native neuronal M-type potassium currents by the anti-convulsant drug retigabine.
    J Neurosci. 2001 Aug 1;21(15):5535-45 PMID: 11466425
  18. Potassium channels Kv1.1, Kv1.2 and Kv1.6 influence excitability of rat visceral sensory neurons.
    J Physiol. 2002 Jun 1;541(Pt 2):467-82 PMID: 12042352
  19. Control of M-current.
    Annu Rev Physiol. 1997;59:483-504 PMID: 9074774
  20. Effects of a cognition-enhancer, linopirdine (DuP 996), on M-type potassium currents (IK(M)) and some other voltage- and ligand-gated membrane currents in rat sympathetic neurons.
    Eur J Neurosci. 1997 Mar;9(3):605-16 PMID: 9104602
  21. Passive and active membrane properties of isolated rat intracardiac neurons: regulation by H- and M-currents.
    J Neurophysiol. 1997 Oct;78(4):1890-902 PMID: 9325358
  22. Experimental and modeling study of Na+ current heterogeneity in rat nodose neurons and its impact on neuronal discharge.
    J Neurophysiol. 1997 Dec;78(6):3198-209 PMID: 9405539
  23. Inhibition of M-current in cultured rat superior cervical ganglia by linopirdine: mechanism of action studies.
    Neuropharmacology. 1997 Nov-Dec;36(11-12):1747-53 PMID: 9517447
  24. Activation kinetics of the delayed rectifier potassium current of bullfrog sympathetic neurons.
    J Neurophysiol. 1998 May;79(5):2345-57 PMID: 9582210
  25. Selectivity of linopirdine (DuP 996), a neurotransmitter release enhancer, in blocking voltage-dependent and calcium-activated potassium currents in hippocampal neurons.
    J Pharmacol Exp Ther. 1998 Aug;286(2):709-17 PMID: 9694925
  26. The KCNQ2 potassium channel: splice variants, functional and developmental expression. Brain localization and comparison with KCNQ3.
    FEBS Lett. 1998 Nov 6;438(3):171-6 PMID: 9827540
  27. Contribution of the hyperpolarization-activated current to the resting membrane potential of rat nodose sensory neurons.
    J Physiol. 1999 Jan 1;514 ( Pt 1):125-38 PMID: 9831721
  28. Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3 K(+) channels that underlie the neuronal M current.
    J Neurosci. 2000 Mar 1;20(5):1710-21 PMID: 10684873
  29. Differential tetraethylammonium sensitivity of KCNQ1-4 potassium channels.
    Br J Pharmacol. 2000 Feb;129(3):413-5 PMID: 10711337
  30. Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors.
    J Physiol. 2000 Feb 1;522 Pt 3:349-55 PMID: 10713961
  31. The novel anticonvulsant retigabine activates M-currents in Chinese hamster ovary-cells tranfected with human KCNQ2/3 subunits.
    Neurosci Lett. 2000 Mar 17;282(1-2):73-6 PMID: 10713399
  32. Redox state dependency of HERGS631C channel pharmacology: relation to C-type inactivation.
    FEBS Lett. 2000 May 26;474(1):111-5 PMID: 10828461
  33. Molecular cloning and functional expression of KCNQ5, a potassium channel subunit that may contribute to neuronal M-current diversity.
    J Biol Chem. 2000 Jul 21;275(29):22395-400 PMID: 10787416
  34. Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine.
    Mol Pharmacol. 2000 Aug;58(2):253-62 PMID: 10908292
  35. KCNQ5, a novel potassium channel broadly expressed in brain, mediates M-type currents.
    J Biol Chem. 2000 Aug 4;275(31):24089-95 PMID: 10816588
  36. Molecular correlates of the M-current in cultured rat hippocampal neurons.
    J Physiol. 2002 Oct 1;544(Pt 1):29-37 PMID: 12356878
  37. Antibodies and a cysteine-modifying reagent show correspondence of M current in neurons to KCNQ2 and KCNQ3 K+ channels.
    Br J Pharmacol. 2002 Dec;137(8):1173-86 PMID: 12466226
  38. Subunit-specific modulation of KCNQ potassium channels by Src tyrosine kinase.
    J Neurosci. 2003 Jan 1;23(1):84-95 PMID: 12514204
  39. Stoichiometry of expressed KCNQ2/KCNQ3 potassium channels and subunit composition of native ganglionic M channels deduced from block by tetraethylammonium.
    J Neurosci. 2003 Jun 15;23(12):5012-9 PMID: 12832524
  40. KCNQ/M currents in sensory neurons: significance for pain therapy.
    J Neurosci. 2003 Aug 6;23(18):7227-36 PMID: 12904483
  41. M channels containing KCNQ2 subunits modulate norepinephrine, aspartate, and GABA release from hippocampal nerve terminals.
    J Neurosci. 2004 Jan 21;24(3):592-7 PMID: 14736843
  42. KCNQ2 is a nodal K+ channel.
    J Neurosci. 2004 Feb 4;24(5):1236-44 PMID: 14762142
  43. KCNQ/M channels control spike afterdepolarization and burst generation in hippocampal neurons.
    J Neurosci. 2004 May 12;24(19):4614-24 PMID: 15140933
  44. Mechanism of block of hEag1 K+ channels by imipramine and astemizole.
    J Gen Physiol. 2004 Oct;124(4):301-17 PMID: 15365094
  45. Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone.
    Nature. 1980 Feb 14;283(5748):673-6 PMID: 6965523
  46. M-currents and other potassium currents in bullfrog sympathetic neurones.
    J Physiol. 1982 Sep;330:537-72 PMID: 6294290
  47. Electrophysiological characterization of a new member of the RCK family of rat brain K+ channels.
    FEBS Lett. 1991 Jan 14;278(1):55-60 PMID: 1993474
  48. Electroclinical signs of benign neonatal familial convulsions.
    Ann Neurol. 1993 Dec;34(6):835-41 PMID: 8250533
  49. 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. 1995 Aug;115(7):1163-8 PMID: 7582539
  50. Modulation and genetic identification of the M channel.
    Prog Biophys Mol Biol. 2000;73(2-4):135-66 PMID: 10958929
Article Info
Journal
The Journal of physiology
Abbr.
J Physiol
ISSN
0022-3751
DOI
10.1113/jphysiol.2006.113308
Published
2006-08-15
Epub
2006-00-15
Pages
175-89
Language
English
Region
England
NLM ID
0266262
PMCID
PMC1819429
Subset
IM
Grants
NHLBI NIH HHS · P01 HL025830 · United States
NHLBI NIH HHS · R01 HL061436 · United States
NHLBI NIH HHS · HL25830 · United States
NHLBI NIH HHS · HL61436 · United States
External Links
PubMed source DOI: 10.1113/jphysiol.2006.113308 PMC Full Text View journal details
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