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Galanin increases membrane excitability and enhances Ca 2+ currents in adult, acutely dissociated dorsal root ganglion neurons
Author(s) -
Kerekes Nóra,
Mennicken Francoise,
O'Donnell Dajan,
Hökfelt Tomas,
Hill Russell H.
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2003.03057.x
Subject(s) - galanin , dorsal root ganglion , chemistry , agonist , neuroscience , neuropeptide , patch clamp , medicine , endocrinology , receptor , biophysics , electrophysiology , biology , sensory system , biochemistry
We examined the effect of galanin (10 −15 –10 −7 m ) on dispersed, mainly small‐sized dorsal root ganglion (DRG) neurons in adult rats using whole‐cell patch‐clamp. Galanin and AR‐M1896, a selective galanin type 2 receptor (GalR2) agonist, both significantly increased the number of action potentials in response to current pulses in 77% of the neurons, indicating an increase in excitability. Galanin also caused a rise in input resistance, decreased the holding current for −60 mV and depolarized the resting potential. In addition, Ca 2+ currents elicited by voltage steps were significantly increased by both galanin and AR‐M1896 in nearly 70% of the cells. This enhancement was observed in 30% of the neurons in the presence of nimodipine or ω‐conotoxin, but in each case ≈ 60% less than without blocking either N‐ or L‐type Ca 2+ channels, indicating modulation of both types of Ca 2+ channels. The percentage of small‐ and medium‐sized neurons expressing GalR2 mRNA in DRGs in situ was similar to that showing increased excitability and Ca 2+ current after galanin application, i.e. ≈ 70–80% of the neurons. The findings suggest that GalR2 has a role in controlling both the excitability, probably by inhibition of GIRK or leak K + channels, and Ca 2+ entry in a large population of presumably nociceptive neurons. The combination of the two effects, which possibly arise from separate biochemical pathways, would increase excitability and enhance intracellular Ca 2+ signalling which would enhance sensory transmission. These mechanisms involving GalR2 receptors may underlie the pronociceptive effects of galanin described in the literature.