A tetrodotoxin-resistant voltage-gated sodium channel from human dorsal root ganglia, hPN3/ SCN10A

• Published in: Pain (Amsterdam) Vol. 78; no. 2; pp. 107 - 114
• Main Authors: Rabert, Douglas K, Koch, Bruce D, Ilnicka, Mariola, Obernolte, Rena A, Naylor, Susan L, Herman, Ronald C, Eglen, Richard M, Hunter, John C, Sangameswaran, Lakshmi
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.11.1998; Elsevier
• Subjects: Amino Acid Sequence - genetics; Animals; Biological and medical sciences; Chromosome Mapping; Cloning, Molecular; Dorsal root ganglia; Electrophysiology; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - metabolism; Human; Humans; Molecular Sequence Data; NAV1.8 Voltage-Gated Sodium Channel; Neuropathic pain; Neuropeptides - genetics; Neuropeptides - metabolism; Neuropeptides - physiology; Oocytes - metabolism; Peripheral nervous system; Sodium channels; Sodium Channels - genetics; Sodium Channels - metabolism; Sodium Channels - physiology; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; Tetrodotoxin; Tissue Distribution; Vertebrates: nervous system and sense organs; Xenopus; Tetrodotoxin; Peripheral nervous system; Human; Sodium channels; Dorsal root ganglia; Neuropathic pain; Spinal cord; Sodium; Central nervous system; Electrophysiology; Sensory neuron; Ionic channel; Spinal ganglion; Ionic current; Molecular cloning; Peripheral neuropathy; In vitro
• ISSN: 0304-3959; 1872-6623
• DOI: 10.1016/S0304-3959(98)00120-1

Neuropathic pain may be produced, at least in part, by the increased activity of primary afferent neurons. Studies have suggested that an accumulation of voltage-gated sodium channels at the site of peripheral nerve injury is a primary precursory event for subsequent afferent hyperexcitability. In this study, a human sodium channel (hPN3, SCN10A) has been cloned from the lumbar 4/5 dorsal root ganglia (DRG). Expression of hPN3 in Xenopus oocytes showed that this clone is a functional voltage-gated sodium channel. The amino acid sequence of hPN3 is most closely related to the rat PN3/SNS sodium channels which are expressed primarily in the small neurons of rat DRGs. The homologous relationship between rPN3 and hPN3 is defined by (i) a high level of sequence identity (ii) sodium currents that are highly resistant to tetrodotoxin (TTX) (iii) similar tissue distribution profiles and (iv) orthologous chromosomal map positions. Since rPN3/SNS has been implicated in nociceptive transmission, hPN3 may prove to be a valuable target for therapeutic agents against neuropathic pain.