Faculty Collaboration Database

GFR alpha2/neurturin signalling regulates noxious heat transduction in isolectin B4-binding mouse sensory neurons. J Physiol 2002 Nov 15;545(1):43-50

Date

11/16/2002

Pubmed ID

12433948

Pubmed Central ID

PMC2290664

DOI

10.1113/jphysiol.2002.027656

Scopus ID

2-s2.0-1842869973 (requires institutional sign-in at Scopus site)   51 Citations

Abstract

The GFR alpha2 receptor is the cognate co-receptor for the neurotrophic factor neurturin and GFR alpha2 is selectively expressed by isolectin B(4) (IB(4))-binding nociceptive sensory neurons. Here, we used two physiological approaches in combination with mice that have a targeted deletion of the GFR alpha2 gene (GFR alpha2 -/- mice) in order to determine whether GFR alpha2/neurturin signalling regulates the functional properties or the survival of IB(4)-binding nociceptors. Because 50 % of IB(4)-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 IB(4)-positive and -negative small-diameter neurons isolated from adult GFR alpha2 -/- and littermate control mice. The percentage of IB(4)-positive neurons that had large (> 100 pA) heat-evoked inward currents was severely reduced in GFR alpha2 -/- 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 IB(4)-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 IB(4)-positive C fibres, was normal. Our data are the first to indicate a transduction-function role for GFR alpha2/neurturin signalling in a specific class of sensory neurons.

Author List

Stucky CL, Rossi J, Airaksinen MS, Lewin GR

Author

Cheryl L. Stucky PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Survival
Cells, Cultured
Drosophila Proteins
Electric Conductivity
Glial Cell Line-Derived Neurotrophic Factor Receptors
Glycoproteins
Hot Temperature
In Vitro Techniques
Lectins
Mice
Mice, Knockout
Nerve Growth Factors
Neurons, Afferent
Neurturin
Nociceptors
Patch-Clamp Techniques
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-ret
Receptor Protein-Tyrosine Kinases
Reference Values
Signal Transduction