Galanin increases membrane excitability and enhances Ca(2+) currents in adult, acutely dissociated dorsal root ganglion neurons.
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 omega-conotoxin, but in each case approximately 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. approximately 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.
Kerekes
Nóra
N
Karolinska Institutet, Department of Neuroscience, Retzius väg 8, SE-17177 Stockholm, Sweden.
Mennicken
Francoise
F
O'Donnell
Dajan
D
Hökfelt
Tomas
T
Hill
Russell H
RH
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D002452:Cell Count; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D017097:Electric Impedance; D019004:Galanin / Q000819:agonists / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology*; D017403:In Situ Hybridization; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D009474:Neurons / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D044091:Receptor, Galanin, Type 1 / Q000378:metabolism; D044092:Receptor, Galanin, Type 2 / Q000235:genetics / Q000378:metabolism; D013460:Sulfur Isotopes / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010446:Peptide Fragments; D012333:RNA, Messenger; D044091:Receptor, Galanin, Type 1; D044092:Receptor, Galanin, Type 2; D013460:Sulfur Isotopes; C434734:galanin (2-11)-amide; D019004:Galanin; D002118:Calcium