Tyrosine kinase A (trkA), the high affinity receptor for nerve growth factor (NGF), is expressed by nociceptive dorsal root ganglion (DRG) neurones with C, Aδ and Aα/β-fibre conduction velocities (CVs). NGF may influence electrophysiological properties of DRG neurones by binding to trkA. Two TTX-resistant (TTX-R) Na channels, Nav1.8 and Nav1.9, are expressed mainly in nociceptors and are associated with their electrophysiological properties: Nav1.8 with high action potential (AP) amplitude and long AP duration and Nav1.9 with long AP duration. To examine whether the influence of NGF on electrophysiological properties of DRG neurones may a) depend on their trkA expression levels and b) result from the influence of NGF on Na channel expression, we studied expression of trkA, Nav1.8 and Nav1.9 in the same physiologically identified DRG neurones in vivo. Young adult female Wistar rats were deeply anaesthetized with an initial dose of 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 the anaesthetic. End-tidal CO2 and blood pressure were monitored throughout. Intracellular recordings were made in lumbar (L4-L6) DRG neurones. After identification of sensory and electrophysiological properties, fluorescent dye was injected into the neurone. Rats were killed with an anaesthetic overdose and perfused through the heart with Zamboni’s fixative. Immunostaining for trkA, Nav1.8 and Nav1.9 was carried out on different frozen sections (7μm) from the same dye-injected DRG neurones. We found significant (P<0.05) positive linear correlations between trkA immunointensity and electrophysiological properties typical of nociceptors, namely: long AP and AHP duration and large AP amplitude in Aα/β-nociceptors (n=20), but not C (n=11) or Aδ (n=13) nociceptors. Similar relationships, again only in Aα/β nociceptors, were found between all these properties and Nav1.8 (n=17) that were significant (P0.05). These findings suggest that, in Aα/β nociceptors, influences of NGF on expression levels of Nav1.8 are related to, and perhaps limited by, expression levels of trkA. This view is supported by a positive correlation between expression of trkA and Nav1.8 in A-fibre nociceptors but not C-fibre nociceptors.
University of Bristol (2005) J Physiol 567P, C60
Oral Communications: Relationship of trkA expression to electrophysiology of Aα/β nociceptive DRG neurones: evidence linking this to Nav1.8 expression
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, Yale University, New Haven, CT, USA.
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Where applicable, experiments conform with Society ethical requirements.