Acute modulation of ASIC3 channels by serotonin contributes to peripheral hyperalgesia
会议名称：《中国神经科学学会第九届全国学术会议暨第五次会员代表大会》
会议日期：2011年
学科分类：0710[理学-生物学] 07[理学] 071006[理学-神经生物学]
关 键 词：acid-sensing ion channel 3 5-HT hyperalgesia
摘 要：正Acid-sensing ion channels（ASICs） are proton-gated cation channels and are emerging as key sensors for extracellular protons in central and peripheral *** currents mediated by ASICs inactivate rapidly even in the continuous presence of agonist（protons）.Remarkably,type 3 ASIC（ASIC3）,which is predominantly distributed in sensory neurons,responds to mild acidosis（pH 6.8-7.2） with a sustained *** characteristics has been proposed to mediate persistent acidic pain associated with arthritis,muscular ischemia,and *** the present study,we investigated acute modulation of ASIC3-containing channels by various inflammatory mediators in both dorsal root ganglia（DRG） neurons and CHO cells expressing ASIC *** found that serotonin（5-HT）,a classical proinflammatory mediator,specifically enhanced the sustained currents of homomeric ASIC3 and heteromeric ASIC3/1b ***,5-HT directly acts on ASIC3 channels rather than through 5-HT receptors, because specific receptor antagonists did not affect 5-HT *** importantly,mutations at ASIC3（E79A, E79S,E423A and Q269A） completely abolished 5-HT-induced ***,co-application of 5-HT and acetic acid significantly increased pain-related behaviors as assayed in the paw-licking test in mice,which was largely attenuated in ASIC3-deletion mice and inhibited by the nonselective ASICs inhibitor amiloride but not by 5-HT receptor antagonists methysergide and *** together,these data identify ASIC3 channels as a molecular target for rapid actions of 5-HT and reinforce the importance of ASIC3 channels in regulating inflammatory pain.