GFR α2/neurturin signalling regulates noxious heat transduction in isolectin B4- binding mouse sensory neurons

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Item Type:	Article
Title:	GFR α2/neurturin signalling regulates noxious heat transduction in isolectin B4- binding mouse sensory neurons
Creators Name:	Stucky, C.L., Rossi, J., Airaksinen, M.S. and Lewin, G.R.
Abstract:	The GFR {alpha}2 receptor is the cognate co-receptor for the neurotrophic factor neurturin and GFR {alpha}2 is selectively expressed by isolectin B4 (IB4)-binding nociceptive sensory neurons. Here, we used two physiological approaches in combination with mice that have a targeted deletion of the GFR {alpha}2 gene (GFR {alpha}2 -/- mice) in order to determine whether GFR {alpha}2/neurturin signalling regulates the functional properties or the survival of IB4-binding nociceptors. Because 50% of IB4-binding neurons respond to noxious heat and because patch clamp recordings of isolated dorsal root ganglion sensory neurons allow one to neurochemically identify subpopulations of neurons, we analysed the noxious heat responsiveness of IB4-positive and -negative small-diameter neurons isolated from adult GFR {alpha}2 -/- and littermate control mice. The percentage of IB4-positive neurons that had large (> 100 pA) heat-evoked inward currents was severely reduced in GFR {alpha}2 -/- mice (12%) compared to wild-type littermates (47%), and this loss in large-magnitude heat currents was accounted for by an increase in neurons with very small (< 100 pA) heat-evoked currents as well as an increase in neurons with no detectable heat current. Counts of IB4-positive and -negative neurons, as well as counts of unmyelinated axons in the saphenous nerve, confirmed that the loss in neurons with large-amplitude heat currents was due to a deficit in heat transduction and not a decrease in cell survival. The effect was modality specific for heat because mechanical transduction of all fibre types, including IB4-positive C fibres, was normal. Our data are the first to indicate a transduction-function role for GFR {alpha}2/neurturin signalling in a specific class of sensory neurons.
Keywords:	Afferent Neurons, Cell Survival, Cultured Cells, Drosophila Proteins, Electric Conductivity, Glial Cell Line-Derived Neurotrophic Factor Receptors, Glycoproteins, Heat, Knockout Mice, Lectins, Nerve Growth Factors, Neurturin, Nociceptors, Patch-Clamp Techniques, Proto-Oncogene Proteins, Proto-Oncogene Proteins C-Ret, Receptor Protein-Tyrosine Kinases, Reference Values, Signal Transduction, Animals, Mice
Source:	Journal of Physiology
ISSN:	0022-3751
Publisher:	Cambridge University Press
Volume:	545
Number:	1
Page Range:	43-50
Date:	November 2002
Official Publication:	https://doi.org/10.1113/jphysiol.2002.027656
PubMed:	View item in PubMed

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