Functional Analysis of a Voltage-Gated Sodium Channel and Its Splice Variant from Rat Dorsal Root Ganglia
Version of Record online: 13 NOV 2002
Journal of Neurochemistry
Volume 70, Issue 6, pages 2262–2272, June 1998
How to Cite
Dietrich, P. S., McGivern, J. G., Delgado, S. G., Koch, B. D., Eglen, R. M., Hunter, J. C. and Sangameswaran, L. (1998), Functional Analysis of a Voltage-Gated Sodium Channel and Its Splice Variant from Rat Dorsal Root Ganglia. Journal of Neurochemistry, 70: 2262–2272. doi: 10.1046/j.1471-4159.1998.70062262.x
- Issue online: 13 NOV 2002
- Version of Record online: 13 NOV 2002
- Received October 24, 1997; revised manuscript received December 19, 1997; accepted December 22, 1997.
- Voltage-gated sodium channel;
- Dorsal root ganglia;
- Xenopus oocyte;
- Tetrodotoxin sensitivity
Abstract: Neurons of the dorsal root ganglia (DRG) express a diversity of voltage-gated sodium channels. From rat DRG we have cloned and functionally expressed a tetrodotoxin-sensitive sodium channel α subunit, NaCh6/Scn8a/rPN4, and a splice variant, rPN4a. Primary structure analysis shows NaCh6/Scn8a/rPN4 to be highly homologous (99%) to NaCh6 and most likely represents the same transcript. The splice variation in rPN4a is homologous in sequence and location to that of rat brain I. Tissue distribution analyzed by RT-PCR showed NaCh6/Scn8a/rPN4 to be expressed at its highest levels in rat brain, at moderate levels in spinal cord, and at lower levels in DRG, nodose ganglia, and superior cervical ganglia and to be absent from sciatic nerve, heart, and skeletal muscle. In contrast, rPN4a shows no expression in brain and low-level expression in spinal cord, whereas in DRG its expression is comparable to that of NaCh6/Scn8a/rPN4. Functional analysis of these channels expressed in Xenopus oocytes showed that NaCh6/Scn8a/rPN4 and rPN4a exhibited similar properties, with V1/2≅−100 mV for steady-state inactivation and V1/2≅−40 mV for activation. rPN4a recovered from inactivation significantly faster than NaCh6/Scn8a/rPN4. NaCh6/Scn8a/rPN4 was inhibited by tetrodotoxin with an IC50≅ 1 nM. Coexpression of the β1 subunit accelerated inactivation kinetics, but the β2 subunit was without effect.