Small-sized dorsal root ganglion (DRG) neurones have been divided into two subgroups: those that bind the isolectin B4 (IB4+) and those that do not (IB4-). The latter group tend to express trkA, the high affinity NGF receptor. We have previously shown that in rat strong IB4 binding is limited to a subgroup of C-fibre nociceptive-type (nociceptive and unresponsive) neurones. In mouse small DRG neurones isolated in vitro, IB4+ neurones had longer somatic action potential (AP) duration and higher densities of TTX-resistant Na+ currents compared with IB4- neurones (Stucky & Lewin, 1999). We have examined whether this pattern holds for APs in C-fibre nociceptive-type DRG neurones in vivo in the rat and if so, whether it is related to expression of two TTX-resistant Na+ channels Nav1.8 and Nav1.9. We therefore made intracellular recordings in vivo in L4-L6 DRG neurones of adult female Wistar rats. The rats were deeply anaesthetized with sodium pentobarbitone (70-80mg/kg, i.p.) and neuromuscularly blocked with regular doses of pancuronium (0.6mg/kg, i.v.) always given with an additional dose (20mg/kg, i.v.) of anaesthetic. End-tidal CO2 and blood pressure were monitored throughout. For each neurone, after recording the somatic AP shape, and recording sensory and electrophysiological properties, fluorescent dye was injected into the soma. The rats were killed with anaesthetic overdose and perfused through the heart with Zamboni’s fixative. Immunostaining to show IB4 binding, Nav1.8 and Nav1.9 was carried out on different frozen sections (7μm) from the same dye-injected DRG neurones. IB4+ C-fibre nociceptive-type neurones were compared with those that were IB4-. They had longer median somatic AP rise times (IB4+ 2.4ms, n=14; IB4- 1.4ms, n=4, P<0.05, Mann Whitney test) and lower median conduction velocities (0.38m/s, n=20; 0.59m/s, n=9, P<0.05). They also had a higher median relative staining intensity for Nav1.9 (67%, n=14; 19%, n=6, P0.05). This confirms that IB4+ C-fibre nociceptive-type neurones have distinct membrane properties from those that are IB4- and suggests that Nav1.9 may contribute to these distinct membrane properties.
University of Bristol (2005) J Physiol 567P, C44
Oral Communications: Distinct electrophysiological properties in vivo of C-fibre nociceptive DRG neurones that bind IB4 relate to the expression of Nav1.9 Na+ channels in rat
Fang, Xin; Djouhri, Laiche; McMullan, Simon; Berry, Carol; Okuse, Kenji; Waxman, Stephen G; Lawson, Sally N;
1. Department of Physiology, University of Bristol, Bristol, Avon, United Kingdom. 2. Hypertension & Stroke Research Laboratory, University of Sydney, Sydney, NSW, Australia. 3. Department of Biology, University College London, London, United Kingdom. 4. Department of Neurology, University of Yale, New Haven, CT, USA.
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