RETRACTED: A Novel Carbamoyloxy Arylalkanoyl Arylpiperazine Compound (SKL-NP) Inhibits Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channel Currents in Rat Dorsal Root Ganglion Neurons (Retracted article. See vol. 16, pg. 367, 2012)

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 (I-n) that plays important roles in neuropathic pain. In small or medium-sized dorsal root ganglion (DRG) neurons (<40 mu m in diameter) exhibiting tonic firing and prominent I-h, SKL-NP inhibited I-h and spike firings in a concentration dependent manner (IC50 = 7.85 mu M) SKL-NP-induced inhibition of I-h 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 I-h 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.