High Throughput Screening Assay for ASIC Channel

Acid-sensing ion channels (ASICs) are members of the amiloride-sensitive epithelial Na+-channel/degenerin superfamily (ENaC/DEG). These ligand-gated ion channels are activated by protons, which are released during tissue acidosis (increase in extracellular acidity). Tissue acidosis, which is evidenced by a drop in extracellular pH, occurs in many acute and chronic pain conditions including inflammation, angina, stroke, ischemic heart disease, arthritis, cancer and traumatic injuries. Protons have been shown to induce pain in humans and it is believed this signal may be mediated by ASICs. This family of channels consists of six isoforms: ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3 and ASIC4. Of the six ASIC subunits ASIC1 (1a/1b) and ASIC3 are attractive targets for the treatment of pain since primary sensory neurons are highly enriched with these channels. These primary afferent fibers are nociceptors that detect and signal painful sensations from the periphery to the brain. ASIC1a and ASIC3 are activated by an acidity range (pH 7.0-6.0) observed in several acute and chronic pain conditions. Moreover, ASIC3 is particularly sensitive to lactic acidosis and thus is considered to be an important component of acidinduced pain response during cardiac and muscle ischemia.

Like many sodium ion channels, ASICs represent challenging targets for high throughput screening. To overcome this issue, Aurora Biomed’s proprietary flux assay approach was successfully applied to this novel ion channel target.

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