(75h) Optical and Electronic Monitoring of Ion Channels Implicated in Pain Sensation Using Biomembrane Bioelectronic Devices

Protein ion channels in cell membranes are a key elements in pain signaling. Around 80 ion channels have strong links to pain sensation, but only a small number of these channels have been successfully drugged for pain management. The opioid crisis only exacerbates the need to understand the underlying causes of pain and find new targets to manage it with minimal side effects. One reason for the bottleneck in discovery of new drugs is the inadequacy of conventional platforms for drug discovery that monitor modulation in ion channel activity. Current methods require a skilled hand, yet are still very laborious, time-consuming, and low throughput. There is an urgent need to develop faster, authentic, and high throughput assays that give direct and quantitative information on ion channel function, drug interactions, and insight on the efficacy of a developed therapy. This presentation will highlight a new technology for the rapid and sensitive measurement of subtle changes in cell membrane permeability and capacitance in response to small molecule interactions with protein ion channels embedded in it. This device features a biomimetic membrane that provides an authentic lipid environment, native cell membrane material to support the natural transmembrane ion channel function, and a sensor made from an electroactive polymer surface upon which the biomembrane is supported. Of focus here is the ATP-gated P2X family ion channels and Trek ion channels. Both ion channel receptors are considered important therapeutic targets for multiple pain modalities including neuropathic, inflammatory, and chronic pain states. This biomembrane sensor is capable of reading and transducing ion fluxes through these ion channels as it depends on the availability of ATP, the presence of specific biomolecules, and drug compounds. Critically, this new sensing platform captures these essential features: 1) it preserves native plasma membrane, protein orientation, fluidity, and activity; 2) is robust and long-lasting; and 3) is compatible with high throughput expansion. The effective treatment of pain remains a challenge as current therapeutics still lack desired levels of efficacy and tolerability. Given the considerable amount of research focus and development on identifying drug targets and engineering new drugs for the treatment of pain, this new biosensing platform may prove to be a useful new approach for drug screening.