PMID- 23554485
OWN - NLM
STAT- MEDLINE
DCOM- 20130528
LR  - 20220129
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 33
IP  - 14
DP  - 2013 Apr 3
TI  - Triple cysteine module within M-type K+ channels mediates reciprocal channel 
      modulation by nitric oxide and reactive oxygen species.
PG  - 6041-6
LID - 10.1523/JNEUROSCI.4275-12.2013 [doi]
AB  - We have identified a new signaling role for nitric oxide (NO) in neurons from the 
      trigeminal ganglia (TG). We show that in rat sensory neurons from the TG the NO 
      donor, S-nitroso-N-acetyl-dl-penicillamine, inhibited M-current. This inhibitory 
      effect was blocked by NO scavenging, while inhibition of NO synthases increased 
      M-current, suggesting that tonic NO levels inhibit M-current in TG neurons. 
      Moreover NO increased neuronal excitability and calcitonin gene-related peptide 
      (CGRP) release and these effects could be prevented by perturbing M-channel 
      function. First, NO-induced depolarization was prevented by pre-application of 
      the M-channel blocker XE991 and second, NO-induced increase in CGRP release was 
      prevented by incubation with the M-channel opener retigabine. We investigated the 
      mechanism of the effects of NO on M-channels and identified a site of action of 
      NO to be the redox modulatory site at the triplet of cysteines within the 
      cytosolic linker between transmembrane domains 2 and 3, which is also a site of 
      oxidative modification of M-channels by reactive oxygen species (ROS). NO and 
      oxidative modifications have opposing effects on M-current, suggesting that a 
      tightly controlled local redox and NO environment will exert fine control over 
      M-channel activity and thus neuronal excitability. Together our data have 
      identified a dynamic redox sensor within neuronal M-channels, which mediates 
      reciprocal regulation of channel activity by NO and ROS. This sensor may play an 
      important role in mediating excitatory effects of NO in such trigeminal disorders 
      as headache and migraine.
FAU - Ooi, Lezanne
AU  - Ooi L
AD  - School of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, United 
      Kingdom. lezanne@uow.edu.au
FAU - Gigout, Sylvain
AU  - Gigout S
FAU - Pettinger, Louisa
AU  - Pettinger L
FAU - Gamper, Nikita
AU  - Gamper N
LA  - eng
GR  - G0700966(82507)/MRC_/Medical Research Council/United Kingdom
GR  - 080593/Z06/Z/WT_/Wellcome Trust/United Kingdom
GR  - G0700966/MRC_/Medical Research Council/United Kingdom
GR  - G1002183/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
GR  - 080593/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone)
RN  - 0 (Aniline Compounds)
RN  - 0 (Anthracenes)
RN  - 0 (Benzoates)
RN  - 0 (Carbamates)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (KCNQ Potassium Channels)
RN  - 0 (KCNQ4 protein, human)
RN  - 0 (Membrane Transport Modulators)
RN  - 0 (Nitric Oxide Donors)
RN  - 0 (Phenylenediamines)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Reactive Oxygen Species)
RN  - 12G01I6BBU (ezogabine)
RN  - 145757-47-7 
      (1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole)
RN  - 29757-24-2 (nitroaniline)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 6SO6U10H04 (Biotin)
RN  - 79032-48-7 (S-Nitroso-N-Acetylpenicillamine)
RN  - JHB2QIZ69Z (Calcitonin Gene-Related Peptide)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - Action Potentials/drug effects/genetics
MH  - Aniline Compounds/pharmacology
MH  - Animals
MH  - Animals, Newborn
MH  - Anthracenes/pharmacology
MH  - Benzoates/pharmacology
MH  - Biotin/metabolism
MH  - Calcitonin Gene-Related Peptide/metabolism
MH  - Carbamates/pharmacology
MH  - Cells, Cultured
MH  - Cysteine/genetics/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - KCNQ Potassium Channels/genetics/*metabolism
MH  - Male
MH  - Membrane Transport Modulators/pharmacology
MH  - Models, Molecular
MH  - Mutation/genetics
MH  - Neurons/drug effects/*physiology
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Donors/pharmacology
MH  - Patch-Clamp Techniques
MH  - Phenylenediamines/pharmacology
MH  - Potassium Channel Blockers/pharmacology
MH  - Rats
MH  - Reactive Oxygen Species/*metabolism
MH  - S-Nitroso-N-Acetylpenicillamine/pharmacology
MH  - Transfection
MH  - Trigeminal Ganglion/cytology
PMC - PMC3664272
MID - EMS52781
OID - NLM: EMS52781
EDAT- 2013/04/05 06:00
MHDA- 2013/05/29 06:00
PMCR- 2013/10/03
CRDT- 2013/04/05 06:00
PHST- 2013/04/05 06:00 [entrez]
PHST- 2013/04/05 06:00 [pubmed]
PHST- 2013/05/29 06:00 [medline]
PHST- 2013/10/03 00:00 [pmc-release]
AID - 33/14/6041 [pii]
AID - 3830056 [pii]
AID - 10.1523/JNEUROSCI.4275-12.2013 [doi]
PST - ppublish
SO  - J Neurosci. 2013 Apr 3;33(14):6041-6. doi: 10.1523/JNEUROSCI.4275-12.2013.