POTASSIUM CHANNEL OPENERS AS AN HYPEREXCITABILITY-REDUCING STRATEGY

Diseases depending on increased electrical excitability, such as epilepsy, pain and cardiac arrhythmia, cause decreased quality of life for the individuals and an enormous burden to the society.

Despite extensive efforts from the pharmaceutical industry in developing ion channel-specific compounds, there has been little success. It is thus a real need for, and a challenge to develop new, better compounds.

Voltage-gated ion channels are at the core of cellular excitability, but most ion channel drugs simply block the pore and fail to reach a more fine-tuned modulation of channel opening. This project aims at exploring new pathways to modulate voltage-gated ion channels.

Our overall, long-term, goal is to develop compounds which can specifically target any voltage-gated ion channel and tune channel function in any desired way.

We have recently identified 150 new strong ion-channel activators, which puts us in a unique position to undertake the proposed project.

The specific goals are to 1) identify compounds that open voltage-gated potassium channels and to explore their sites and mechanisms of action, to 2) develop compounds that selectively target specific voltage-gated ion channels, and to 3) develop compounds that selectively target specific ion-channel parameters to cause desired effects.

The proposed project, if it succeeds, can revolutionize therapeutics for all types of ion-channel associated diseases.