Abstract
Acid-sensing ion channels (ASICs) are proton-gated cation channels and key mediators of responses to neuronal injury. ASICs exhibit unique patterns of distribution in the brain, with high expression in neurons and low expression in glial cells. While there has been a lot of focus on ASIC in neurons, less is known about the roles of ASICs in glial cells. ASIC1a is expressed in astrocytes and might contribute to synaptic transmission and long-term potentiation. In oligodendrocytes, constitutive activation of ASIC1a participates in demyelinating diseases. ASIC1a, ASIC2a, and ASIC3, found in microglial cells, could mediate the inflammatory response. Under pathological conditions, ASIC dysregulation in glial cells can contribute to disease states. For example, activation of astrocytic ASIC1a may worsen neurodegeneration and glioma staging, activation of microglial ASIC1a and ASIC2a may perpetuate ischemia and inflammation, while oligodendrocytic ASIC1a might be involved in multiple sclerosis. This review concentrates on the unique ASIC components in each of the glial cells and integrates these glial-specific ASICs with their physiological and pathological conditions. Such knowledge provides promising evidence for targeting of ASICs in individual glial cells as a therapeutic strategy for a diverse range of conditions.
Highlights
Acid-sensing ion channels (ASICs) are proton-gated cation channels found extensively in the nervous system [1,2]
Research focused on ASIC1a in astrocytes of gliomas may provide a direction in determining cellular targets to prevent cancer progression
In cerebellar neurons with much less ASIC2 expression, ASIC2 deletion had no effect on surface ASIC1a level, acid-activated current density, or acidosis/ischemia-induced neuronal injury, suggesting that heteromeric ASIC1a/2 channels in certain brain regions are likely to contribute to ischemic brain injury [108]
Summary
Acid-sensing ion channels (ASICs) are proton-gated cation channels found extensively in the nervous system [1,2]. Other non-proton ligands have been shown to activate these channels at a physiological pH (e.g., pH 7.4) including the exogenous agent, 2-guanidine-4-methylquinazoline (GMQ), which has been found to activate ASIC3 [23,24], and the coral snake toxin, MitTx, which activates ASIC1 [25]. A toxin isolated from black mamba snakes, has been shown to strongly inhibit ASIC1 channels [37,38]. The availability of these select inhibitors has facilitated the dissection of their role in distinct cellular processes [39]
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