PMID- 24402080
OWN - NLM
STAT- MEDLINE
DCOM- 20141124
LR  - 20211021
IS  - 1432-1912 (Electronic)
IS  - 0028-1298 (Linking)
VI  - 387
IP  - 4
DP  - 2014 Apr
TI  - Electrophysiology and pharmacology of tandem domain potassium channel TREK-1 
      related BDNF synthesis in rat astrocytes.
PG  - 303-12
LID - 10.1007/s00210-013-0952-2 [doi]
AB  - In the present study, the functional properties and pharmacology of two-pore 
      domain potassium channel (K2P) TREK-1 in primary cultured rat brain astrocytes 
      were investigated. Western blot, patch clamping techniques, and ELISA were used 
      to detect the distribution and function of TREK-1 as well as the expression of 
      brain-derived neurotrophic factor (BDNF) on the primary cultured astrocytes. It 
      was shown that TREK-1 protein expressed in astrocytes was 2.4-fold higher than it 
      was expressed in microglia. Single channel recording via patch clamping showed 
      that the TREK-1 outward currents in astrocytes could be activated by arachidonic 
      acid (AA) or chloroform with the conductance of 113 +/- 14 and 120 +/- 13 pS, 
      respectively. The current was also sensitive to mechanical stretch and 
      intracellular acidification. Negative pressure (-30 cm H2O) and acidification of 
      intracellular solution (pH 6.8 or 6.3) both enhanced TREK-1 channel open 
      probability significantly. Further pharmacological studies showed that TREK-1 
      antagonist penfluridol inhibited AA-induced currents, and both penfluridol and 
      methionine (TREK-1 blockers) significantly increased BDNF level in astrocytes by 
      50 %. These results indicated that TREK-1 channel current was a major component 
      of K2P currents in astrocytes. TREK-1 channels might play important roles in 
      regulating the function of astrocytes and might be used as a drug target for 
      neuroprotection.
FAU - Lu, Li
AU  - Lu L
AD  - State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, No. 1 Xiannongtan Street, Xicheng District, Beijing, 100050, 
      China.
FAU - Wang, Weiping
AU  - Wang W
FAU - Peng, Ying
AU  - Peng Y
FAU - Li, Jiang
AU  - Li J
FAU - Wang, Ling
AU  - Wang L
FAU - Wang, Xiaoliang
AU  - Wang X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140109
PL  - Germany
TA  - Naunyn Schmiedebergs Arch Pharmacol
JT  - Naunyn-Schmiedeberg's archives of pharmacology
JID - 0326264
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Potassium Channels, Tandem Pore Domain)
RN  - 0 (potassium channel protein TREK-1)
RN  - 25TLU22Q8H (Penfluridol)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 7V31YC746X (Chloroform)
SB  - IM
MH  - Animals
MH  - Arachidonic Acid/pharmacology
MH  - Astrocytes/*physiology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cells, Cultured
MH  - Chloroform/pharmacology
MH  - Microglia/*physiology
MH  - Penfluridol
MH  - Potassium Channels, Tandem Pore Domain/agonists/antagonists & 
      inhibitors/*physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Stress, Mechanical
EDAT- 2014/01/10 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/01/10 06:00
PHST- 2013/10/11 00:00 [received]
PHST- 2013/12/18 00:00 [accepted]
PHST- 2014/01/10 06:00 [entrez]
PHST- 2014/01/10 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - 10.1007/s00210-013-0952-2 [doi]
PST - ppublish
SO  - Naunyn Schmiedebergs Arch Pharmacol. 2014 Apr;387(4):303-12. doi: 
      10.1007/s00210-013-0952-2. Epub 2014 Jan 9.