Dual Effect of Exogenous Nitric Oxide on Neuronal Excitability in Rat Substantia Gelatinosa Neurons

A-Reum Park,Hae In Lee,Dejidnorov Semjid,Do Kyung Kim,Sang Woo Chun

doi:10.1155/2014/628531

Abstract

Nitric oxide (NO) is an important signaling molecule involved in nociceptive transmission. It can induce analgesic and hyperalgesic effects in the central nervous system. In this study, patch-clamp recording was used to investigate the effect of NO on neuronal excitability in substantia gelatinosa (SG) neurons of the spinal cord. Different concentrations of sodium nitroprusside (SNP; NO donor) induced a dual effect on the excitability of neuronal membrane: 1 mM of SNP evoked membrane hyperpolarization and an outward current, whereas 10 µM induced depolarization of the membrane and an inward current. These effects were prevented by hemoglobin and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt (c-PTIO) (NO scavengers), phenyl N-tert-butylnitrone (PBN; nonspecific reactive oxygen species scavenger), and through inhibition of soluble guanylyl cyclase (sGC). Pretreatment with n-ethylmaleimide (NEM; thiol-alkylating agent) also decreased effects of both 1 mM and 10 µM SNP, suggesting that these responses were mediated by direct S-nitrosylation. Charybdotoxin (CTX) and tetraethylammonium (TEA) (large-conductance Ca2+-activated K+ channel blockers) and glybenclamide (ATP-sensitive K+ channel blocker) decreased SNP-induced hyperpolarization. La3+ (nonspecific cation channel blocker), but not Cs+ (hyperpolarization-activated K+ channel blocker), blocked SNP-induced membrane depolarization. In conclusion, NO dually affects neuronal excitability in a concentration-dependent manner via modification of various K+ channels.

Highlights

Nitric oxide (NO) is a pivotal signaling molecule involved in many diverse developmental and physiological processes in the mammalian nervous system [1,2,3]
We investigated the effects of NO scavengers to determine whether the sodium nitroprusside (SNP)-induced changes in membrane potential were due to the release of NO from the donor
To determine whether the SNP-evoked responses involved the direct modulation of membrane proteins by NO, we examined the effect of NEM, which blocks sulfhydryl groups, on substantia gelatinosa (SG) neurons

Summary

Introduction

Nitric oxide (NO) is a pivotal signaling molecule involved in many diverse developmental and physiological processes in the mammalian nervous system [1,2,3]. NO donors as well as endogenously produced NO play a role in many physiological processes, including smooth muscle relaxation, cellular proliferation, apoptosis, neurotransmitter release, and cell differentiation [6]. Oxidative stress due to reactive oxygen species (ROS) such as O2∙−, hydrogen peroxide (H2O2), NO, and ONOO− interferes with normal cell function and can cause cell damage. NO has a dual role in the regulation of pain processes; it can mediate a nociceptive or induce an antinociceptive effect. NO, produced in the NOS-containing spinal cord neurons, plays a pivotal role in chronic pain [14, 15]

Methods

Results

Conclusion