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First published on December 17, 2004; DOI: 10.1124/mol.104.010173

0026-895X/05/6703-585-588$20.00
Mol Pharmacol 67:585-588, 2005

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PERSPECTIVE

Activators of Cation Channels: Potential in Treatment of Channelopathies

Guiscard Seebohm

Institute of Physiology I, University of Tuebingen, Tuebingen, Germany

Cation channels are membrane proteins that provide controlled pathways for ion passage through cellular membranes. They play important roles in physiological processes such as secretory transduction, control of ion homeostasis, cell volume, vesicle cycling, and electrical control of excitable tissues. In a variety of channelopathies, ion channel function is reduced, and activators of cation channels are promising candidates to regain channel function in acquired or inherited channelopathies. Shortage in cation channel activators prevents testing of efficiency of activators in a variety of indications. This shortage might result from the relative incapability of modern drug screening methods, but increasing knowledge about cation channel activator binding and action might enable us in the future to use in silico-guided drug design of channel modulators. New compounds such as the HERG channel activator (3R,4R)-4-[3-(6-methoxy-quinolin-4-yl)-3-oxo-propyl]-1-[3-(2,3,5-trifluoro-phenyl)-prop-2-ynyl]-piperidine-3-carboxylic acid (RPR260243) will enable us to increase our understanding in cation channel modulation and to test the concept of channel activation as a clinically relevant principle in treatment of channelopathies.

Received December 9, 2004; accepted December 16, 2004

Address correspondence to: Dr. Guiscard Seebohm, Physiologisches Institut 1, Universität Tuebingen, Gmelinstr. 5, D-72076 Tuebingen, Germany. E-mail: guiscard.seebohm{at}gmx.de




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