PMID- 30356026
OWN - NLM
STAT- MEDLINE
DCOM- 20190115
LR  - 20190115
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 19
IP  - 11
DP  - 2018 Oct 24
TI  - Inwardly Rectifying Potassium Channel Kir4.1 as a Novel Modulator of BDNF 
      Expression in Astrocytes.
LID - 10.3390/ijms19113313 [doi]
LID - 3313
AB  - Brain-derived neurotrophic factor (BDNF) is a key molecule essential for neural 
      plasticity and development, and is implicated in the pathophysiology of various 
      central nervous system (CNS) disorders. It is now documented that BDNF is 
      synthesized not only in neurons, but also in astrocytes which actively regulate 
      neuronal activities by forming tripartite synapses. Inwardly rectifying potassium 
      (Kir) channel subunit Kir4.1, which is specifically expressed in astrocytes, 
      constructs Kir4.1 and Kir4.1/5.1 channels, and mediates the spatial potassium 
      (K(+)) buffering action of astrocytes. Recent evidence illustrates that Kir4.1 
      channels play important roles in bringing about the actions of antidepressant 
      drugs and modulating BDNF expression in astrocytes. Although the precise 
      mechanisms remain to be clarified, it seems likely that inhibition 
      (down-regulation or blockade) of astrocytic Kir4.1 channels attenuates K(+) 
      buffering, increases neuronal excitability by elevating extracellular K(+) and 
      glutamate, and facilitates BDNF expression. Conversely, activation (up-regulation 
      or opening) of Kir4.1 channels reduces neuronal excitability by lowering 
      extracellular K(+) and glutamate, and attenuates BDNF expression. Particularly, the 
      former pathophysiological alterations seem to be important in epileptogenesis and 
      pain sensitization, and the latter in the pathogenesis of depressive disorders. 
      In this article, we review the functions of Kir4.1 channels, with a focus on 
      their regulation of spatial K(+) buffering and BDNF expression in astrocytes, and 
      discuss the role of the astrocytic Kir4.1-BDNF system in modulating CNS 
      disorders.
FAU - Ohno, Yukihiro
AU  - Ohno Y
AD  - Department of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 
      Nasahara, Takatsuki, Osaka 569-1094, Japan. yohno@gly.oups.ac.jp.
FAU - Kinboshi, Masato
AU  - Kinboshi M
AD  - Department of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 
      Nasahara, Takatsuki, Osaka 569-1094, Japan. kinboshi@kuhp.kyoto-u.ac.jp.
FAU - Shimizu, Saki
AU  - Shimizu S
AD  - Department of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 
      Nasahara, Takatsuki, Osaka 569-1094, Japan. s.shimizu@gly.oups.ac.jp.
LA  - eng
GR  - 17K08324/Ministry of Education, Culture, Sports, Science and Technology/
GR  - 15H04892/Ministry of Education, Culture, Sports, Science and Technology/
GR  - 16K21501/Ministry of Education, Culture, Sports, Science and Technology/
PT  - Journal Article
PT  - Review
DEP - 20181024
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Kcnj10 (channel))
RN  - 0 (Potassium Channels, Inwardly Rectifying)
SB  - IM
MH  - Animals
MH  - Astrocytes/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism
MH  - Depressive Disorder/*metabolism
MH  - Epilepsy/*metabolism
MH  - Humans
MH  - Neurons/metabolism/physiology
MH  - Potassium Channels, Inwardly Rectifying/chemistry/genetics/*metabolism
PMC - PMC6274740
OTO - NOTNLM
OT  - Kir4.1 channels
OT  - astrocytes
OT  - brain-derived neurotrophic factor (BDNF), depressive disorders
OT  - epilepsy
OT  - pain
OT  - spatial potassium buffering
COIS- The authors declare no conflict of interest.
EDAT- 2018/10/26 06:00
MHDA- 2019/01/16 06:00
PMCR- 2018/11/01
CRDT- 2018/10/26 06:00
PHST- 2018/09/24 00:00 [received]
PHST- 2018/10/19 00:00 [revised]
PHST- 2018/10/22 00:00 [accepted]
PHST- 2018/10/26 06:00 [entrez]
PHST- 2018/10/26 06:00 [pubmed]
PHST- 2019/01/16 06:00 [medline]
PHST- 2018/11/01 00:00 [pmc-release]
AID - ijms19113313 [pii]
AID - ijms-19-03313 [pii]
AID - 10.3390/ijms19113313 [doi]
PST - epublish
SO  - Int J Mol Sci. 2018 Oct 24;19(11):3313. doi: 10.3390/ijms19113313.