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.