I. Cellular and molecular biology of sodium channel beta-subunits: therapeutic implications for pain?
Voltage-gated sodium channel alpha-subunits have been shown to be key mediators of the pathophysiology of pain. The present review considers the role of sodium channel auxiliary beta-subunits in channel modulation, channel protein expression levels, and interactions with extracellular matrix and cytoskeletal signaling molecules. Although beta-subunits have not yet been directly implicated in pain mechanisms, their intimate association with and ability to regulate alpha-subunits predicts that they may be a viable target for therapeutic intervention in the future. It is proposed that multifunctional sodium channel beta-subunits provide a critical link between extracellular and intracellular signaling molecules and thus have the ability to fine tune channel activity and electrical excitability.
Isom
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Department of Pharmacology, The University of Michigan, Ann Arbor, Michigan 48109-0632, USA. lisom@umich.edu
D000818:Animals; D017487:Ankyrins / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002468:Cell Physiological Phenomena; D003001:Cloning, Molecular; D058966:Contactins; D053503:Epithelial Sodium Channels; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D009437:Neuralgia / Q000378:metabolism; D010146:Pain / Q000235:genetics / Q000503:physiopathology*; D059408:Pain Management; D012333:RNA, Messenger / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D014781:Viscera / Q000503:physiopathology*
D017487:Ankyrins; D015816:Cell Adhesion Molecules, Neuronal; D058966:Contactins; D053503:Epithelial Sodium Channels; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D015222:Sodium Channels