PMID- 29358904
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 10
DP  - 2017
TI  - Inhibition of Inwardly Rectifying Potassium (Kir) 4.1 Channels Facilitates 
      Brain-Derived Neurotrophic Factor (BDNF) Expression in Astrocytes.
PG  - 408
LID - 10.3389/fnmol.2017.00408 [doi]
LID - 408
AB  - Inwardly rectifying potassium (Kir) 4.1 channels in astrocytes regulate neuronal 
      excitability by mediating spatial potassium buffering. Although dysfunction of 
      astrocytic Kir4.1 channels is implicated in the development of epileptic 
      seizures, the functional mechanisms of Kir4.1 channels in modulating 
      epileptogenesis remain unknown. We herein evaluated the effects of Kir4.1 
      inhibition (blockade and knockdown) on expression of brain-derived neurotrophic 
      factor (BDNF), a key modulator of epileptogenesis, in the primary cultures of 
      mouse astrocytes. For blockade of Kir4.1 channels, we tested several 
      antidepressant agents which reportedly bound to and blocked Kir4.1 channels in a 
      subunit-specific manner. Treatment of astrocytes with fluoxetine enhanced BDNF 
      mRNA expression in a concentration-dependent manner and increased the BDNF 
      protein level. Other antidepressants (e.g., sertraline and imipramine) also 
      increased the expression of BDNF mRNA with relative potencies similar to those 
      for inhibition of Kir4.1 channels. In addition, suppression of Kir4.1 expression 
      by the transfection of small interfering RNA (siRNA) targeting Kir4.1 
      significantly increased the mRNA and protein levels of BDNF. The BDNF induction 
      by Kir4.1 siRNA transfection was suppressed by the MEK1/2 inhibitor U0126, but 
      not by the p38 MAPK inhibitor SB202190 or the JNK inhibitor SP600125. The present 
      results demonstrated that inhibition of Kir4.1 channels facilitates BDNF 
      expression in astrocytes primarily by activating the Ras/Raf/MEK/ERK pathway, 
      which may be linked to the development of epilepsy and other neuropsychiatric 
      disorders.
FAU - Kinboshi, Masato
AU  - Kinboshi M
AD  - Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, 
      Japan.
AD  - Department of Neurology, Wakayama Medical University, Wakayama, Japan.
AD  - Department of Epilepsy, Movement Disorders and Physiology, Graduate School of 
      Medicine, Kyoto University, Kyoto, Japan.
FAU - Mukai, Takahiro
AU  - Mukai T
AD  - Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, 
      Japan.
FAU - Nagao, Yuki
AU  - Nagao Y
AD  - Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, 
      Japan.
FAU - Matsuba, Yusuke
AU  - Matsuba Y
AD  - Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, 
      Japan.
FAU - Tsuji, Yoshimi
AU  - Tsuji Y
AD  - Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, 
      Japan.
FAU - Tanaka, Shiho
AU  - Tanaka S
AD  - Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, 
      Japan.
FAU - Tokudome, Kentaro
AU  - Tokudome K
AD  - Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, 
      Japan.
AD  - Department of Molecular and Cellular Pharmacology, Graduate School of Medicine, 
      Osaka University, Osaka, Japan.
FAU - Shimizu, Saki
AU  - Shimizu S
AD  - Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, 
      Japan.
FAU - Ito, Hidefumi
AU  - Ito H
AD  - Department of Neurology, Wakayama Medical University, Wakayama, Japan.
FAU - Ikeda, Akio
AU  - Ikeda A
AD  - Department of Epilepsy, Movement Disorders and Physiology, Graduate School of 
      Medicine, Kyoto University, Kyoto, Japan.
FAU - Inanobe, Atsushi
AU  - Inanobe A
AD  - Department of Molecular and Cellular Pharmacology, Graduate School of Medicine, 
      Osaka University, Osaka, Japan.
FAU - Kurachi, Yoshihisa
AU  - Kurachi Y
AD  - Department of Molecular and Cellular Pharmacology, Graduate School of Medicine, 
      Osaka University, Osaka, Japan.
FAU - Inoue, Seiji
AU  - Inoue S
AD  - Education and Research Center for Fundamental Pharmaceutical Sciences, Osaka 
      University of Pharmaceutical Sciences, Osaka, Japan.
FAU - Ohno, Yukihiro
AU  - Ohno Y
AD  - Laboratory of Pharmacology, Osaka University of Pharmaceutical Sciences, Osaka, 
      Japan.
LA  - eng
PT  - Journal Article
DEP - 20171207
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
PMC - PMC5768989
OTO - NOTNLM
OT  - BDNF
OT  - Kir4.1 channels
OT  - antidepressants
OT  - astrocytes
OT  - epilepsy
EDAT- 2018/01/24 06:00
MHDA- 2018/01/24 06:01
PMCR- 2017/01/01
CRDT- 2018/01/24 06:00
PHST- 2017/08/17 00:00 [received]
PHST- 2017/11/24 00:00 [accepted]
PHST- 2018/01/24 06:00 [entrez]
PHST- 2018/01/24 06:00 [pubmed]
PHST- 2018/01/24 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2017.00408 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2017 Dec 7;10:408. doi: 10.3389/fnmol.2017.00408. eCollection 
      2017.