ION CHANNELS AS DRUG TARGETS
Ions generally cannot move freely across cell membranes, but must enter or exit a cell through pores created by ion channels. Ion channels open and close, or gate, in response to particular stimuli, including ions, other cellular factors, changes in electrical voltage or drugs. Two ion channels in either open or closed states are depicted in the cartoon below.
The concentration of specific ions in particular cells in the body is critically important to many vital physiological functions. Consequently, ion channels play a key role in a wide variety of processes in the human body, which can be broadly grouped into three categories:
- Electrical impulse generation and conduction along nerves in the central and peripheral nervous system, the heart and other organs;
- Fluid balance within cells and across cell membranes, including fluid balance in red blood cells, cells in the eye and other cells throughout the body;
- Signal transduction within and among cells, including immune system cells that, when activated, trigger an inflammatory response.
Small molecule compounds have been shown to both activate and inhibit ion channels. As a result, ion channels represent an important class of targets for pharmaceutical intervention in a broad range of disease areas. Examples of currently marketed drugs that exert their effects through ion channel modulation include calcium channel blockers, such as Norvasc and verapamil, which are used for the treatment of hypertension and various other cardiovascular disorders; sodium channel blockers, such as Lamictal, which is used for the treatment of epilepsy, and lidocaine, a local anesthetic; and potassium channel blockers, such as Glipizide, which is used in the treatment of diabetes. Additionally, novel ion channels recently discovered by Icagen or uncovered by the human genome effort provide a broadened opportunity for discoveries of new drugs for almost all medical disorders.
Ion channels are also attractive therapeutic targets because they play crucial roles in all functions and pathophysiological processes in the human body. Icagen utilizes ion channel modulators to target specific tissues or cells within a tissue. The specificity of these modulators is such that they will differentiate among physiological states (open, closed or inactivated) of the target channels. Since the activity of ion channels is based on conformational changes, drugs can be tailored to work only when they are needed.
For more information on ion channels and how they work, check out Rockefeller University Interactive Explorations.
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