PMID- 22348007
OWN - NLM
STAT- MEDLINE
DCOM- 20120731
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 2
DP  - 2012
TI  - Inhibition of post-synaptic Kv7/KCNQ/M channels facilitates long-term 
      potentiation in the hippocampus.
PG  - e30402
LID - 10.1371/journal.pone.0030402 [doi]
LID - e30402
AB  - Activation of muscarinic acetylcholine receptors (mAChR) facilitates the 
      induction of synaptic plasticity and enhances cognitive function. In the 
      hippocampus, M(1) mAChR on CA1 pyramidal cells inhibit both small conductance 
      Ca(2+)-activated KCa2 potassium channels and voltage-activated Kv7 potassium 
      channels. Inhibition of KCa2 channels facilitates long-term potentiation (LTP) by 
      enhancing Ca(2+)calcium influx through postsynaptic NMDA receptors (NMDAR). 
      Inhibition of Kv7 channels is also reported to facilitate LTP but the mechanism 
      of action is unclear. Here, we show that inhibition of Kv7 channels with XE-991 
      facilitated LTP induced by theta burst pairing at Schaffer collateral commissural 
      synapses in rat hippocampal slices. Similarly, negating Kv7 channel conductance 
      using dynamic clamp methodologies also facilitated LTP. Negation of Kv7 channels 
      by XE-991 or dynamic clamp did not enhance synaptic NMDAR activation in response 
      to theta burst synaptic stimulation. Instead, Kv7 channel inhibition increased 
      the amplitude and duration of the after-depolarisation following a burst of 
      action potentials. Furthermore, the effects of XE-991 were reversed by 
      re-introducing a Kv7-like conductance with dynamic clamp. These data reveal that 
      Kv7 channel inhibition promotes NMDAR opening during LTP induction by enhancing 
      depolarisation during and after bursts of postsynaptic action potentials. Thus, 
      during the induction of LTP M(1) mAChRs enhance NMDAR opening by two distinct 
      mechanisms namely inhibition of KCa2 and Kv7 channels.
FAU - Petrovic, Milos M
AU  - Petrovic MM
AD  - Medical Research Council Centre for Synaptic Plasticity, School of Physiology and 
      Pharmacology, University of Bristol, Bristol, United Kingdom.
FAU - Nowacki, Jakub
AU  - Nowacki J
FAU - Olivo, Valeria
AU  - Olivo V
FAU - Tsaneva-Atanasova, Krasimira
AU  - Tsaneva-Atanasova K
FAU - Randall, Andrew D
AU  - Randall AD
FAU - Mellor, Jack R
AU  - Mellor JR
LA  - eng
GR  - Wellcome Trust/United Kingdom
GR  - 085354/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120213
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (KCNQ1 Potassium Channel)
RN  - 0 (Receptors, Muscarinic)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Action Potentials
MH  - Animals
MH  - Calcium/metabolism
MH  - Hippocampus/*physiology
MH  - KCNQ1 Potassium Channel/*antagonists & inhibitors
MH  - Long-Term Potentiation/*physiology
MH  - Rats
MH  - Receptors, Muscarinic
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
PMC - PMC3278412
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/02/22 06:00
MHDA- 2012/08/01 06:00
PMCR- 2012/02/13
CRDT- 2012/02/21 06:00
PHST- 2011/08/30 00:00 [received]
PHST- 2011/12/20 00:00 [accepted]
PHST- 2012/02/21 06:00 [entrez]
PHST- 2012/02/22 06:00 [pubmed]
PHST- 2012/08/01 06:00 [medline]
PHST- 2012/02/13 00:00 [pmc-release]
AID - PONE-D-11-17089 [pii]
AID - 10.1371/journal.pone.0030402 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(2):e30402. doi: 10.1371/journal.pone.0030402. Epub 2012 Feb 13.