PMID- 22083644
OWN - NLM
STAT- MEDLINE
DCOM- 20120618
LR  - 20211021
IS  - 1432-2013 (Electronic)
IS  - 0031-6768 (Linking)
VI  - 463
IP  - 1
DP  - 2012 Jan
TI  - Identification of the muscarinic pathway underlying cessation of sleep-related 
      burst activity in rat thalamocortical relay neurons.
PG  - 89-102
LID - 10.1007/s00424-011-1056-9 [doi]
AB  - Modulation of the standing outward current (I (SO)) by muscarinic acetylcholine 
      (ACh) receptor (MAChR) stimulation is fundamental for the state-dependent change 
      in activity mode of thalamocortical relay (TC) neurons. Here, we probe the 
      contribution of MAChR subtypes, G proteins, phospholipase C (PLC), and two pore 
      domain K(+) (K(2P)) channels to this signaling cascade. By the use of spadin and 
      A293 as specific blockers, we identify TWIK-related K(+) (TREK)-1 channel as new 
      targets and confirm TWIK-related acid-sensitve K(+) (TASK)-1 channels as known 
      effectors of muscarinic signaling in TC neurons. These findings were confirmed 
      using a high affinity blocker of TASK-3 and TREK-1, namely, tetrahexylammonium 
      chloride. It was found that the effect of muscarinic stimulation was inhibited by 
      M(1)AChR-(pirenzepine, MT-7) and M(3)AChR-specific (4-DAMP) antagonists, 
      phosphoinositide-specific PLCbeta (PI-PLC) inhibitors (U73122, ET-18-OCH(3)), but 
      not the phosphatidylcholine-specific PLC (PC-PLC) blocker D609. By comparison, 
      depleting guanosine-5'-triphosphate (GTP) in the intracellular milieu nearly 
      completely abolished the effect of MAChR stimulation. The block of TASK and TREK 
      channels was accompanied by a reduction of the muscarinic effect on I (SO). 
      Current-clamp recordings revealed a membrane depolarization following MAChR 
      stimulation, which was sufficient to switch TC neurons from burst to tonic firing 
      under control conditions but not during block of M(1)AChR/M(3)AChR and in the 
      absence of intracellular GTP. These findings point to a critical role of G 
      proteins and PLC as well as TASK and TREK channels in the muscarinic modulation 
      of thalamic activity modes.
FAU - Bista, Pawan
AU  - Bista P
AD  - Institut fur Physiologie I, Westfalische Wilhelms-Universitat, Robert-Koch-Str. 
      27a, 48149, Munster, Germany.
FAU - Meuth, Sven G
AU  - Meuth SG
FAU - Kanyshkova, Tatyana
AU  - Kanyshkova T
FAU - Cerina, Manuela
AU  - Cerina M
FAU - Pawlowski, Matthias
AU  - Pawlowski M
FAU - Ehling, Petra
AU  - Ehling P
FAU - Landgraf, Peter
AU  - Landgraf P
FAU - Borsotto, Marc
AU  - Borsotto M
FAU - Heurteaux, Catherine
AU  - Heurteaux C
FAU - Pape, Hans-Christian
AU  - Pape HC
FAU - Baukrowitz, Thomas
AU  - Baukrowitz T
FAU - Budde, Thomas
AU  - Budde T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111115
PL  - Germany
TA  - Pflugers Arch
JT  - Pflugers Archiv : European journal of physiology
JID - 0154720
RN  - 0 (Kcnk9 protein, rat)
RN  - 0 (Muscarinic Agonists)
RN  - 0 (Muscarinic Antagonists)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Potassium Channels, Tandem Pore Domain)
RN  - 0 (Receptor, Muscarinic M1)
RN  - 0 (Receptor, Muscarinic M3)
RN  - 0 (Thionucleotides)
RN  - 0 (potassium channel protein TREK-1)
RN  - 146-91-8 (Guanosine Diphosphate)
RN  - 1HQ3YCN4GS (potassium channel subfamily K member 3)
RN  - 5RY0UWH1JL (Oxotremorine)
RN  - 63939-65-1 (oxotremorine M)
RN  - 71376-97-1 (guanosine 5'-O-(2-thiodiphosphate))
RN  - 7T101UWZ5W (Muscarine)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - EC 3.1.4.11 (Phospholipase C beta)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gq-G11)
SB  - IM
MH  - Action Potentials/drug effects/*physiology
MH  - Animals
MH  - Cholinergic Neurons/drug effects/*physiology
MH  - Electrophysiological Phenomena/drug effects/physiology
MH  - GTP-Binding Protein alpha Subunits, Gq-G11/genetics
MH  - Gene Expression/genetics
MH  - Guanosine Diphosphate/analogs & derivatives/pharmacology
MH  - Guanosine Triphosphate/antagonists & inhibitors/metabolism
MH  - Hydrogen-Ion Concentration
MH  - Lateral Thalamic Nuclei/cytology/physiology
MH  - Membrane Potentials/drug effects/physiology
MH  - Muscarine/pharmacology
MH  - Muscarinic Agonists/pharmacology
MH  - Muscarinic Antagonists/pharmacology
MH  - Nerve Tissue Proteins
MH  - Oxotremorine/analogs & derivatives/pharmacology
MH  - Patch-Clamp Techniques
MH  - Phospholipase C beta/antagonists & inhibitors/genetics/metabolism
MH  - Potassium Channels, Tandem Pore Domain/antagonists & 
      inhibitors/genetics/metabolism
MH  - Rats
MH  - Rats, Long-Evans
MH  - Receptor, Muscarinic M1/agonists/antagonists & inhibitors/genetics/metabolism
MH  - Receptor, Muscarinic M3/antagonists & inhibitors/genetics/metabolism
MH  - Signal Transduction/drug effects/*physiology
MH  - Sleep/*physiology
MH  - Thalamus/cytology/*physiology
MH  - Thionucleotides/pharmacology
EDAT- 2011/11/16 06:00
MHDA- 2012/06/19 06:00
CRDT- 2011/11/16 06:00
PHST- 2011/08/23 00:00 [received]
PHST- 2011/10/26 00:00 [accepted]
PHST- 2011/10/19 00:00 [revised]
PHST- 2011/11/16 06:00 [entrez]
PHST- 2011/11/16 06:00 [pubmed]
PHST- 2012/06/19 06:00 [medline]
AID - 10.1007/s00424-011-1056-9 [doi]
PST - ppublish
SO  - Pflugers Arch. 2012 Jan;463(1):89-102. doi: 10.1007/s00424-011-1056-9. Epub 2011 
      Nov 15.