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
Center for Biological Research, Neurobiology Unit, Roche Bioscience, 3401 Hillview Avenue, Palo Alto, CA 94304, USA Department of Cellular and Structural Biology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78284, USA Formerly of Syntex (USA) Inc, 3401 Hillview Avenue, Palo Alto, CA 94304, USA.
Pain. 1998 Nov;78(2):107-114. 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.
神经性疼痛至少部分是由初级传入神经元活动增加所引起的。研究表明，电压门控钠通道在周围神经损伤部位的积聚是随后传入神经兴奋性过高的主要先兆事件。在本研究中，从腰4/5背根神经节（DRG）克隆出了一种人类钠通道（hPN3，SCN10A）。hPN3在非洲爪蟾卵母细胞中的表达表明，该克隆体是一种功能性电压门控钠通道。hPN3的氨基酸序列与主要在大鼠背根神经节的小神经元中表达的大鼠PN3/SNS钠通道最为密切相关。rPN3和hPN3之间的同源关系由以下几点确定：（i）高度的序列同一性；（ii）对河豚毒素（TTX）具有高度抗性的钠电流；（iii）相似的组织分布图谱；（iv）直系染色体图谱位置。由于rPN3/SNS与伤害性感受传递有关，hPN3可能被证明是抗神经性疼痛治疗药物的一个有价值的靶点。
