Identification of PN1, a predominant voltage-dependent sodium channel expressed principally in peripheral neurons

Abstract

Membrane excitability in different tissues is due, in large part, to the selective expression of distinct genes encoding the voltage-dependent sodium channel. Although the predominant sodium channels in brain, skeletal muscle, and cardiac muscle have been identified, the major sodium channel types responsible for excitability within the peripheral nervous system have remained elusive. We now describe the deduced primary structure of a sodium channel, peripheral nerve type 1 (PN1), which is expressed at high levels throughout the peripheral nervous system and is targeted to nerve terminals of cultured dorsal root ganglion neurons. Studies using cultured PC12 cells indicate that both expression and targeting of PN1 is induced by treatment of the cells with nerve growth factor. The preferential localization suggests that the PN1 sodium channel plays a specific role in nerve excitability.

Size Matters: Erythromelalgia Mutation S241T in Nav1.7 Alters Channel Gating

“…Because Nav1.4 is mainly expressed in skeletal muscle cells (54,55), whereas Nav1.7 is expressed in sensory neurons and sympathetic neurons (13)(14)(15), it is not surprising that these analogous mutations in Nav1.4 and Nav1.7 have different functional effects. As shown recently, cell background can have a significant influence on the effects of mutant ion-channel electrogenesis (17).…”

“…Recently, IEM was linked to mutations in the voltage-gated sodium channel Nav1.7 (8 -12). Nav1.7 is preferentially expressed in dorsal root and sympathetic ganglion neurons (13)(14)(15).…”

Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain

“…Its presence at high levels in the growth cones of small-diameter neurons (9,11) suggests that it is likely to play some role in the transmission of nociceptive information. Immunochemical studies of sensory neurons in guinea pigs supports the view that Na v 1.7 is associated with nociceptors (12).…”

“…Na v 1.7 was first cloned from the pheochromocytoma PC12 cell line (9,10). Its presence at high levels in the growth cones of small-diameter neurons (9,11) suggests that it is likely to play some role in the transmission of nociceptive information.…”

Gain-of-function mutation of a voltage-gated sodium channel NaV1.7 associated with peripheral pain and impaired limb development

“…The Na V 1.7 2 sodium channel is preferentially expressed in sensory and sympathetic neurons (1)(2)(3)(4) and their axons (5). Na V 1.7 is expressed in small neurons in dorsal root ganglion (DRG), giving rise to unmyelinated peripheral nerve fibers, which have a functional role in pain signal propagation from receptive fields to the first synapse in the dorsal horn of the spinal cord (3,4).…”