Constitutively Open Voltage-Gated K+ Channels and Methods for Discovering Modulators Thereof
Description of Invention:
This technology relates to materials and methods for developing high throughput strategies for discovery of both inhibitors and activators of voltage-gated potassium channels. Voltage gated potassium channels are important regulators of electrical excitability throughout the nervous system, vascular and cardiac smooth muscle, and various secretory tissues such as the pancreas. Drugs that modulate the activity of these receptors could have applications in a variety of therapeutic areas involving abnormal electrical activity, including epilepsy, stroke, cardiac arrhythmia, hypertension, and diabetes.
The technology described here involves the identification of mutations in voltage-gated potassium channels that effectively lock the pore open at all membrane potentials. Previously, it has not been possible to develop yeast-based high throughput screens using voltage-gated potassium channels because these channels are normally closed at the negative membrane potentials associated with yeast.
In addition, other types of high-throughput screens for K channel inhibitors and activators use voltage-sensitive dyes or indicators as reporters of K channel activity. Mutations that lock voltage-gated K channels open at negative voltages could significantly improved the sensitivity of these voltage-sensitive screens. The strategy employed to lock open voltage-gated potassium channels involves alterations in an area of the protein that is conserved in all voltage-gated potassium channels, and should therefore be applicable to all such potassium channels. This will allow generally for the development of high-throughput screens for activators and inhibitors of all voltage-gated potassium channels.
Inventors:
Drs. Kenton J. Swartz and David H. Hackos (NINDS)
Patent Status:
DHHS Reference No. E-286-1999/0 Licensing Status: This technology is no longer available for licensing.
Portfolios: Internal Medicine Central Nervous System
Central Nervous System -Therapeutics-Neurological Therapeutics-Anticonvulsants Central Nervous System -Therapeutics-Neurological Therapeutics-Stroke Internal Medicine-Diagnostics-Cardiology-In Vivo Central Nervous System -Therapeutics Central Nervous System -Research Materials Internal Medicine-Diagnostics
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