PMID- 19463897
OWN - NLM
STAT- MEDLINE
DCOM- 20090824
LR  - 20181201
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 461
IP  - 1
DP  - 2009 Sep 11
TI  - The facilitating effect of systemic administration of Kv7/M channel blocker XE991 
      on LTP induction in the hippocampal CA1 area independent of muscarinic 
      activation.
PG  - 25-9
LID - 10.1016/j.neulet.2009.05.042 [doi]
AB  - A large amount of in vitro studies demonstrate suppression of M-current in 
      hippocampal neurons by Kv7/M channel blocker results in depolarization of 
      membrane potential and release of neurotransmitters, such as acetylcholine and 
      glutamate, suggesting that Kv7/M channel may play important roles in regulating 
      synaptic plasticity. In the present study, we examined the in vivo effect of 
      Kv7/M channel inhibition on the long-term potentiation (LTP) induction at basal 
      dendrites in hippocampal CA1 area of urethane-anaesthetized rats. The Kv7/M 
      channel was inhibited by intraperitoneal injection of XE991 (10mg/kg) and the LTP 
      of field excitatory postsynaptic potential (fEPSP) was induced by supra-threshold 
      high frequency stimulation (S1 HFS). A weak protocol which was just below the 
      threshold for evoking LTP was used as sub-threshold high frequency stimulation 
      (S2 HFS). XE991 did not significantly alter the slope of fEPSP and the magnitude 
      of LTP induced by S1 HFS, suggesting that Kv7/M channel inhibition had little or 
      no effect on glutamatergic transmission under basal conditions. However, XE991 
      could make S2 HFS evoke LTP even after the application of the muscarinic 
      cholinergic (mACh) receptor antagonist scopolamine, suggesting that Kv7/M channel 
      inhibition lowered the threshold for LTP induction and the effect was independent 
      of muscarinic activation. Based on the above findings, we concluded that the 
      facilitating effect of XE991 on LTP induction is not mediated by its ability to 
      enhance the release of acetylcholine; therefore, Kv7/M channel blockers may 
      provide a therapeutic benefit to cholinergic deficiency-related cognitive 
      impairment, e.g., Alzheimer's disease.
FAU - Song, Ming-Ke
AU  - Song MK
AD  - Department of Pharmacology, Institutes of Medical Sciences, Shanghai Jiao Tong 
      University School of Medicine, 280 South Chongqing Road, Shanghai 200025, PR 
      China.
FAU - Cui, Yong-Yao
AU  - Cui YY
FAU - Zhang, Wei-Wei
AU  - Zhang WW
FAU - Zhu, Liang
AU  - Zhu L
FAU - Lu, Yang
AU  - Lu Y
FAU - Chen, Hong-Zhuan
AU  - Chen HZ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090520
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone)
RN  - 0 (Anthracenes)
RN  - 0 (KCNQ2 Potassium Channel)
RN  - 0 (KCNQ3 Potassium Channel)
RN  - 0 (Muscarinic Antagonists)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Receptors, Muscarinic)
RN  - DL48G20X8X (Scopolamine)
SB  - IM
MH  - Animals
MH  - Anthracenes/*pharmacology
MH  - Dendrites/physiology
MH  - Electric Stimulation
MH  - Excitatory Postsynaptic Potentials
MH  - Hippocampus/*drug effects/physiology
MH  - KCNQ2 Potassium Channel/*antagonists & inhibitors
MH  - KCNQ3 Potassium Channel/*antagonists & inhibitors
MH  - *Long-Term Potentiation
MH  - Male
MH  - Muscarinic Antagonists/pharmacology
MH  - Potassium Channel Blockers/*pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Muscarinic/*physiology
MH  - Scopolamine/pharmacology
MH  - Synapses/physiology
EDAT- 2009/05/26 09:00
MHDA- 2009/08/25 09:00
CRDT- 2009/05/26 09:00
PHST- 2009/01/21 00:00 [received]
PHST- 2009/04/30 00:00 [revised]
PHST- 2009/05/15 00:00 [accepted]
PHST- 2009/05/26 09:00 [entrez]
PHST- 2009/05/26 09:00 [pubmed]
PHST- 2009/08/25 09:00 [medline]
AID - S0304-3940(09)00666-1 [pii]
AID - 10.1016/j.neulet.2009.05.042 [doi]
PST - ppublish
SO  - Neurosci Lett. 2009 Sep 11;461(1):25-9. doi: 10.1016/j.neulet.2009.05.042. Epub 
      2009 May 20.