1. Department of Biology, University College London, Gower Street, London WC1E 6BT, UK
2. Molecular Neurobiology Program, Skirball Institute for Biomolecular Medicine, Departments of Cell Biology and Physiology and Neuroscience, New York University School of Medicine, New York, New York 10016, USA

Correspondence to: John N. Wood¹ Correspondence and requests for materials should be addressed to J.N.W. (e-mail: Email: J.Wood@ucl.ac.uk).

Abstract

The tetrodotoxin-resistant sodium channel Na_V1.8/SNS is expressed exclusively in sensory neurons and appears to have an important role in pain pathways^{1, 2}. Unlike other sodium channels, Na_V1.8 is poorly expressed in cell lines even in the presence of accessory -subunits³. Here we identify annexin II light chain^{4, 5} (p11) as a regulatory factor that facilitates the expression of Na_V1.8. p11 binds directly to the amino terminus of Na_V1.8 and promotes the translocation of Na_V1.8 to the plasma membrane, producing functional channels. The endogenous Na_V1.8 current in sensory neurons is inhibited by antisense downregulation of p11 expression. Because direct association with p11 is required for functional expression of Na_V1.8, disrupting this interaction may be a useful new approach to downregulating Na_V1.8 and effecting analgesia⁶.