Ion channels are membrane proteins that allow the selective movement of charged molecules through cellularmembranes. Many disease states, such as cystic fibrosis, muscular dystrophies, hypertension, and cardiac arrhythmiasare caused by ion channel pathologies. Ion channels have been identified by the drug discovery industry as excellenttargets for therapeutic intervention but because of the technical hurdles involved in developing quality, high-throughput functional ion channel assays, the development of 'ion channel drugs' has been disappointing.Photoswitch Biosciences has developed technology, which allows attaching small nanomachines to ion channelsenabling rapid and reversible control of these proteins by light. These 'photoswitched' ion channels allow us to non-invasively control cell membrane potential and, hence, the activity of voltage-dependent ion channels.The Specific Aim for the Phase I component of this fast track SBIR project are: (1) Demonstrate the feasibility ofusing extracellular electric field recording as a membrane potential readout. Our original plan was to use voltage-sensitive dyes for this application, but recent results from our lab suggests that extracellular recording of electricalfield potentials may offer a variety of benefits, including instrument design and assay simplicity. The Phase II goalsare to build three fully functional prototype screening systems consisting of instruments, engineered cell lines,reagents, and software. The use of the hybrid method of extracellular field potential recording technology coupledwith photoswitch technology for ion channel assays has several advantages over existing techniques: (1) Eliminationof liquid additions for channel activation, (2) Highly scalable for high-throughput ion channel drug discovery, (3)Price per data point is at least 100X less than automated electrophysiology, (4) Channel activation is almost 100Xfaster than KCl addition. The ability to rapidly depolarize and repolarize cells in a high-throughput format isespecially important for the discovery of 'use-dependent' compounds that achieve target selectivity via affecting onlythe channels that are active. This breakthrough technology will finally allow the full exploitation of ion channels asdrug targets.
Thesaurus Terms: Action Potentials;Affect;Arrhythmia;Assay Development;Award;Base;Behavior;Biological Assay;Budgets;Calcium Channel;Cell Adhesion;Cell Line;Cell Membrane;Cells;Cellular Membrane;Charge;Commercialization;Computer Software;Coupled;Cystic Fibrosis;Data;Design;Detection;Development;Disease;Dose;Drug Discovery;Drug Targeting;Dyes;Economics;Electric Field;Electrodes;Electrophysiology (Science);Engineering;Equipment Design;Event;Extracellular;Falls;Fluorescence Resonance Energy Transfer;Funding;Goals;Heart;Hybrids;Hypertension;Industry;Inhibitory Concentration 50;Instrument;Instrumentation;Interest;Ion Channel;Light;Lighting;Liquid Substance;Measurement;Measures;Mediating;Membrane Potentials;Membrane Proteins;Methods;Movement;Muscle;Muscular Dystrophies;Nanomachine;Nervous System Structure;Neurons;Noise;Novel;Operation;Optics;Pathology;Pathway Interactions;Performance;Pharmaceutical Preparations;Phase;Physiological;Price;Procedures;Programs;Proteins;Prototype;Public Health Relevance;Reagent;Reporting;Response;Scheme;Screening;Signal Transduction;Small Business Innovation Research Grant;Sodium Channel;Software Development;Source;Stable Cell Line;Success;System;Techniques;Technology;Testing;Therapeutic Intervention;Voltage;Whole-Cell Recordings;Work;
