کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8840603 | 1614690 | 2018 | 32 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Acid Sensing Ion Channel 1a (ASIC1a) Mediates Activity-induced Pain by Modulation of Heteromeric ASIC Channel Kinetics
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کلمات کلیدی
DRGHEPESEGTAMWTASIC4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid - 4- (2-hydroxyethyl) -1-piperazineethanesulfonic acidethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid - اتیلن گلیکول بیس (β-آمینویل اتر) -N، N، N '، N'-tetraacetic اسیدCho - برایChinese Hamster Ovary - تخمدان هامستر چینیAcid - تیز آب، اسیدFatigue - خستگیPain - دردexercise - ورزشHyperalgesia - پردردی یا هایپرآلژزیAcid sensing ion channels - کانال های یونی حساس به اسیدdorsal root ganglia - گانگلیس ریشه پشتی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Chronic muscle pain is acutely worsened by exercise. Acid sensing ion channels (ASIC) are heteromeric channels expressed in muscle sensory neurons that detect decreases in pH. We have previously shown ASIC3 is important in activity-induced hyperalgesia. However, ASICs form heteromers with ASIC1a being a key component in sensory neurons. Therefore, we studied the role of ASIC1a in mice using behavioral pharmacology and genetic deletion in a model of activity-induced hyperalgesia. We found ASIC1aâ/â mice developed mechanical hyperalgesia similar to wild-type mice, but antagonism of ASIC1a, with psalmotoxin, prevented development of mechanical hyperalgesia in wild-type mice, but not in ASIC1aâ/â mice. To explain this discrepancy, we then performed electrophysiology studies of ASICs and examined the effects of psalmotoxin on ASIC heteromers. We expressed ASIC1a, 2 and 3 heteromers or ASIC1 and 3 heteromers in CHO cells, and examined the effects of psalmotoxin on pH sensitivity. Psalmotoxin significantly altered the properties of ASIC hetomeric channels. Specifically, in ASIC1a/2/3 heteromers, psalmotoxin slowed the kinetics of desensitization, slowed the recovery from desensitization, and inhibited pH-dependent steady-state desensitization, but had no effect on pH-evoked current amplitudes. We found a different pattern in ASIC1a/3 heteromers. There was a significant leftward shift in the pH dose response of steady-state desensitization and decrease in pH-evoked current amplitudes. These results suggest that blockade of ASIC1a modulates the kinetics of heteromeric ASICs to prevent development of activity-induced hyperalgesia. These data suggest ASIC1a is a key subunit in heteromeric ASICs and may be a pharmacological target for treatment of musculoskeletal pain.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 386, 21 August 2018, Pages 166-174
Journal: Neuroscience - Volume 386, 21 August 2018, Pages 166-174
نویسندگان
Nicholas S. Gregory, Mamta Gautam, Christopher J. Benson, Kathleen A. Sluka,