Pharmacological regulation of ion channels by auxiliary subunits.
Ion channels link environmental stimuli to intracellular signaling pathways. Channel proteins often occur in macromolecular complexes in association with auxiliary subunits that control channel trafficking, gating and pharmacology. A large number of drugs exert their therapeutic effects by regulating ion channel activity and downstream signaling. These drugs can target either the principle ion channel or the associated auxiliary subunits. Sulfonylurea-type antidiabetics and gabapentin-type anticonvulsants exemplify important therapeutics that bind to ion channel auxiliary subunits. The recent molecular characterization of neuronal glutamate receptor ion channel complexes identified auxiliary subunits and associated proteins that may provide new targets for treating psychiatric and neurodegenerative diseases.
Kato
Akihiko S
AS
Neuroscience Discovery, Lilly Research Laboratories, Eli Lilly & Co, Indianapolis, IN 46285, USA. kato_akihiko@lilly.com
Bredt
David S
DS
D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D007473:Ion Channels / Q000378:metabolism*; D011485:Protein Binding; D021122:Protein Subunits