Abstract
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.
Highlights
Astrocytes are the most abundant glial cells and play important roles in maintaining the integrity of brain functions
Astrocytes are implicated in the pathogenesis of various disorders including schizophrenia, major depressive disorders, Parkinson’s disease, Alzheimer’s disease, epilepsy, and chronic pain [7,8,9]
To confirm the above hypothesis, we investigated the effects of Kir4.1 channel inhibition on expression of neurotrophic factors in cultured astrocytes [9]
Summary
Astrocytes are the most abundant glial cells and play important roles in maintaining the integrity of brain functions. Elevated expression of BDNF is implicated in the pathogenesis of epilepsy and chronic pain sensitization whereas the neurotrophic property of BDNF is expected to restore neurodegenerative. 2018, 19, 3313 and chronic pain sensitization whereas the neurotrophic property of BDNF is expected to restore neurodegenerative disordersdisease such as Parkinson’s disease andEarly. Recent evidence illustrates that astrocytic BDNF expression is recent evidence illustrates that astrocytic BDNF expression is modulated by the inwardly modulated by the inwardly rectifying potassium (Kir) 4.1 channels, +which mediate the rectifying potassium (Kir). 4.1 channels, which mediate the spatial potassium (K ) buffering function spatial potassium (K+) buffering function of astrocytes and regulate neuronal activities [9,18]. Role of the astrocytic Kir4.1-BDNF system in modulating central nervous system (CNS) disorders
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