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Content archived on 2024-04-30

Development of a yeast-based model system for expression of higher eukaryotic K-Channels and their pharmacological analysis

Objective



Transmembrane ion channels regulate the movement of ions (particularly Na+, K+, Ca2+ and Cl-) across cellular membranes, and are critical to numerous aspects of neurobiology. Cells express a diverse array of ion-channel proteins that vary widely in their ion selectivity and in their modulation by ligands (such as neurotransmitters) or by membrane voltage. Potassium is the most abundant cellular cation and the imbalance of potassium across the cell membrane is responsible for the maintenance of the membrane potential. Activation of different K+ selective ion channels is essential to control the excitability of nerve and muscle cells. Considerable interest has been focused on the roles of potassium channels in shaping the physiological behaviours of both excitable and non-excitable cells. Pharmacological tools, such as inhibitors have been used to characterize individual classes of channels but for many potassium channels specific blockers are not available. Heterologous expression of ion channel proteins in yeast provides an alternative to animal testing for functional (pharmacological) analysis as well as providing a robust, cell-based system for rapid identification of new lead compounds. K+-channel modulators are valuable pharmacological tools with therapeutic potential.The cloning and characterization of the yeast K+ transport system, and most recently, of the outward rectifying K+channel enabled the generation of yeast mutants lacking those transporters and channels. This advance has made possible new approaches for the analysis of mammalian K+ selective channels by functional complementation of yeast mutants. The development of a yeast-based expression and screening system will play a key role in the development of in-vitro pharmacological tests for chemical and pharmacological agents.The development of a yeast screening systems provides useful tools both for academic and industrial applications in an EC wide strategy.

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Coordinator

Rheinische Friedrich-Wilhelms-Universität Bonn
EU contribution
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Address
Kirschallee 1
53115 Bonn
Germany

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Participants (5)

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