Modulations of Na v 1.8 and Na v 1.9 Channels in Monosodium Urate-Induced Gouty Arthritis in Mice.

Autor: Qiu J; Department of Clinical Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing City, 210009, Jiangsu Province, China., Xu X; Department of Clinical Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing City, 210009, Jiangsu Province, China., Zhang S; School of Pharmacy, Xuzhou Medical University, Xuzhou City, 221100, Jiangsu Province, China., Li G; Key Laboratory of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Research of Southwest Medical University, 6463000, Luzhou City, Sichuan Province, China., Zhang G; Department of Clinical Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing City, 210009, Jiangsu Province, China. njzhanggq@163.com.
Jazyk: angličtina
Zdroj: Inflammation [Inflammation] 2021 Aug; Vol. 44 (4), pp. 1405-1415. Date of Electronic Publication: 2021 Jan 29.
DOI: 10.1007/s10753-021-01425-y
Abstrakt: The aim of the present study was to observe the changes of TTX-R, Na v 1.8, and Na v 1.9 Na + currents in MSU-induced gouty arthritis mice, and to explore the possibility of Na v 1.8 and Na v 1.9 channels as potential targets for gout pain treatment. Acute gouty arthritis was induced by monosodium urate (MSU) in mice. Swelling degree was evaluated by measuring the circumference of the ankle joint. Mechanical allodynia was assessed by applying the electronic von Frey. Na + currents were recorded by patch-clamp techniques in acute isolated dorsal root ganglion (DRG) neurons. MSU treatment significantly increased the swelling degree of ankle joint and decreased the mechanical pain threshold. The amplitude of TTX-R Na + current was significantly increased and reached its peak on the 4th day after injection of MSU. For TTX-R Na + channel subunits, Na v 1.8 current density was significantly increased, but Na v 1.9 current density was markedly decreased after MSU treatment. MSU treatment shifted the steady-state activation curves of TTX-R Na + channel, Na v 1.8 and Na v 1.9 channels, and the inactivation curves of TTX-R Na + channel and Na v 1.8 channels to the depolarizing direction, but did not affect the inactivation curve of Na v 1.9 channel. Compared with the normal group, the recovery of Na v 1.8 channel was faster, while that of Na v 1.9 channel was slower. The recovery of TTX-R Na + channel remained unchanged after MSU treatment. Additionally, MSU treatment increased DRG neurons excitability by reducing action potential threshold. Na v 1.8 channel, not Na v 1.9 channel, may be involved in MSU-induced gout pain by increasing nerve excitability.
(© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)
Databáze: MEDLINE
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