A Novel Carbamoyloxy Arylalkanoyl Arylpiperazine Compound (SKL-NP) Inhibits Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channel Currents in Rat Dorsal Root Ganglion Neurons.
10.4196/kjpp.2012.16.4.237
- Author:
Gehoon CHUNG
1
;
Tae Hyung KIM
;
Hyewon SHIN
;
Eunhee CHAE
;
Hanju YI
;
Hongsik MOON
;
Hyun Jin KIM
;
Joong Soo KIM
;
Sung Jun JUNG
;
Seog Bae OH
Author Information
1. National Research Laboratory for Pain, Dental Research Institute and Department of Neurobiology and Physiology, School of Dentistry, Seoul National University, Seoul 110-749, Korea.
- Publication Type:Retracted Publication ; Original Article
- Keywords:
cAMP;
Gi-protein;
Hyperpolarization-activated cyclic nucleotide-gated channel;
Ih;
Neuropathic pain
- MeSH:
Animals;
Diagnosis-Related Groups;
Ethylmaleimide;
Fires;
Ganglia, Spinal;
Membranes;
Neuralgia;
Neurons;
Pertussis Toxin;
Rats;
Spinal Nerve Roots
- From:The Korean Journal of Physiology and Pharmacology
2012;16(4):237-241
- CountryRepublic of Korea
- Language:English
-
Abstract:
In this study, we determined mode of action of a novel carbamoyloxy arylalkanoyl arylpiperazine compound (SKL-NP) on hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents (Ih) that plays important roles in neuropathic pain. In small or medium-sized dorsal root ganglion (DRG) neurons (<40 microm in diameter) exhibiting tonic firing and prominent Ih, SKL-NP inhibited Ih and spike firings in a concentration dependent manner (IC50=7.85 microM). SKL-NP-induced inhibition of Ih was blocked by pretreatment of pertussis toxin (PTX) and N-ethylmaleimide (NEM) as well as 8-Br-cAMP, a membrane permeable cAMP analogue. These results suggest that SKL-NP modulates Ih in indirect manner by the activation of a Gi-protein coupled receptor that decreases intracellular cAMP concentration. Taken together, SKL-NP has the inhibitory effect on HCN channel currents (I h) in DRG neurons of rats.
