Acid-sensing ion channels (ASICs): therapeutic targets for neurological diseases and their regulation

Abstract

Extracellular acidification occurs not only in pathologicalconditions such as inflammation and brain ischemia, but alsoin normal physiological conditions such as synaptic transmission.Acid-sensing ion channels (ASICs) can detect a broadrange of physiological pH changes during pathological andsynaptic cellular activities. ASICs are voltage-independent,proton-gated cation channels widely expressed throughout thecentral and peripheral nervous system. Activation of ASICs isinvolved in pain perception, synaptic plasticity, learning andmemory, fear, ischemic neuronal injury, seizure termination,neuronal degeneration, and mechanosensation. Therefore,ASICs emerge as potential therapeutic targets for manipulatingpain and neurological diseases. The activity of these channelscan be regulated by many factors such as lactate, Zn2+, andPhe-Met-Arg-Phe amide (FMRFamide)-like neuropeptides byinteracting with the channel’s large extracellular loop. ASICsare also modulated by G protein-coupled receptors such asCB1 cannabinoid receptors and 5-HT2. This review focuses onthe physiological roles of ASICs and the molecularmechanisms by which these channels are regulated. [BMBReports 2013; 46(6): 295-304]

Keywords

• Acidosis
• Acid-sensing ion channels
• G protein-coupled receptors
• Modulation
• Pain
• pH