Persistent inflammation alters the density and distribution of voltage-activated calcium channels in subpopulations of rat cutaneous DRG neurons.
The impact of persistent inflammation on voltage-activated Ca(2+) channels in cutaneous DRG neurons from adult rats was assessed with whole cell patch clamp techniques, sqRT-PCR and Western blot analysis. Inflammation was induced with a subcutaneous injection of complete Freund's adjuvant (CFA). DiI was used to identify DRG neurons innervating the site of inflammation. Three days after CFA injection, high threshold Ca(2+) current (HVA) density was significantly reduced in small and medium, but not large diameter neurons, reflecting a decrease in N-, L- and P/Q-type currents. This decrease in HVA current was associated with an increase in mRNA encoding the α2δ1-subunit complex, but no detectable change in N-type subunit (Ca(V)2.2) mRNA. An increase in both α2δ1 and Ca(V)2.2 protein was detected in the central nerves arising from L4 and L5 ganglia ipsilateral to the site of inflammation. In current clamp experiments on small and medium diameter cutaneous DRG neurons from naïve rats, blocking ∼40% of HVA current with Cd(2+) (5μM), had opposite effects on subpopulations of cutaneous DRG neurons (increasing excitability and action potential duration in some and decreasing excitability in others). The alterations in the density and distribution of voltage-activated Ca(2+) channels in subpopulations of cutaneous DRG neurons that develop following CFA injection should contribute to changes in sensory transmission observed in the presence of inflammation.
Lu
Shao-Gang
SG
Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA 15213, USA Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15213, USA The Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA 15213, USA Department of Anesthesiology & Perioperative Care, School of Medicine, University of California, Irvine, CA 92697, USA.
Zhang
Xiu-Lin
XL
Luo
David Z
DZ
Gold
Michael S
MS
D000200:Action Potentials / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D015220:Calcium Channels / Q000378:metabolism*; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism
D015220:Calcium Channels