NOVEL SIMPLE SCREEN FOR POTASSIUM CHANNELS

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DESCRIPTION (Adapted from the application): Chan Test Inc. is a drug testing company that provides customized contract services for lead screening of ion channels. Based on their experience over the past three years Chan Test has developed successful protocols that meet the unique needs of each of their customers. Because their protocols and contract services are now established for lead screening and because the pharmaceutical industry is very interested in voltage-dependent K+ (Kv) channels as targets for development of new drugs, the time is ripe to develop a novel high throughput screen for these channels. This additional capability will extend their range of services and enhance their lead screening business in two ways, first by increasing their client base and second by providing more candidate drugs for lead screening. Kv channels are therapeutic targets for cardiac arrhythmias, stroke, hypertension heart failure, asthma, diabetes, irritable colon, gastro-esophageal reflux disorders, urinary incontinence, epilepsy, migraine and neuropsychiatric disorders. In this Phase I SBIR they will test the feasibility of a novel, simple screen that they are developing using genetic engineering of a protist species. The innovative feature is that the species will be dependent for growth on extracellular K+ concentrations that will also activate Kv channels. The readout is simple: growth or no growth. The effects of the genetic engineering will be monitored by Southern analysis and electrophysiological recording of membrane currents. The channels to be examined initially will be the Human Ether-A-GO-GO related Gene (HERG) product and as a control, the human inwardly rectifying K+ channel Kir 2.2. HERG was selected because it is: 1) critical to cardiac repolarization, 2) the main target for class III cardiac antiarrhythmic drugs, and 3) mutated in hereditary along QT syndrome. Other Kv channels will be tested subsequently. In Phase II they will implement the high throughput features of the screen. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE