التفاصيل البيبلوغرافية
| العنوان: |
Dexmedetomidine inhibits Tetrodotoxin-resistant Nav1.8 sodium channel activity through Gi/o-dependent pathway in rat dorsal root ganglion neurons |
| المؤلفون: |
Gu, Xi-Yao, Liu, Ben-Long, Zang, Kai-Kai, Yang, Liu, Xu, Hua, Pan, Hai-Li, Zhao, Zhi-Qi, Zhang, Yu-Qiu |
| بيانات النشر: |
BioMed Central Ltd. |
| سنة النشر: |
2015 |
| المجموعة: |
BioMed Central |
| مصطلحات موضوعية: |
α2-adrenoceptor, Dexmedetomidine, Dorsal root ganglion, Pain, Tetrodotoxin-resistant (TTX-R) sodium channel Nav1.8, Whole-cell recording |
| الوصف: |
Background Systemically administered dexmedetomidine (DEX), a selective α2 adrenergic receptor (α2-AR) agonists, produces analgesia and sedation. Peripherally restricted α2-AR antagonist could block the analgesic effect of systemic DEX on neuropathic pain, with no effect on sedation, indicating peripheral analgesic effect of DEX. Tetrodotoxin-resistant (TTX-R) sodium channel Na v 1.8 play important roles in the conduction of nociceptive sensation. Both α2-AR and Nav1.8 are found in small nociceptive DRG neurons. We, therefore, investigated the effects of DEX on the Na v 1.8 currents in acutely dissociated small-diameter DRG neurons. Results Whole-cell patch-clamp recordings demonstrated that DEX concentration-dependently suppressed TTX-R Na v 1.8 currents in small-diameter lumbar DRG neurons. DEX also shifted the steady-state inactivation curves of Na v 1.8 in a hyperpolarizing direction and increased the threshold of action potential and decrease electrical and chemical stimuli-evoked firings in small-diameter DRG neurons. The α2-AR antagonist yohimbine or α2 A -AR antagonist BRL44408 but not α2 B -AR antagonist imiloxan blocked the inhibition of Na v 1.8 currents by DEX. Immunohistochemistry results showed that Na v 1.8 was predominantly expressed in peripherin-positive small-diameter DRG neurons, and some of them were α2 A -AR-positive ones. Our electrophysiological recordings also demonstrated that DEX-induced inhibition of Na v 1.8 currents was prevented by intracellular application of G-protein inhibitor GDPβ-s or G i/o proteins inhibitor pertussis toxin (PTX), and bath application of adenylate cyclase (AC) activator forskolin or membrane-permeable cAMP analogue 8-Bromo-cAMP (8-Br-cAMP). PKA inhibitor Rp-cAMP could mimic DEX-induced inhibition of Na v 1.8 currents. Conclusions We established a functional link between α2-AR and Na v 1.8 in primary sensory neurons utilizing the G i/o /AC/cAMP/PKA pathway, which probably mediating peripheral analgesia of DEX. |
| نوع الوثيقة: |
report |
| اللغة: |
English |
| العلاقة: |
http://www.molecularbrain.com/content/8/1/15Test |
| الإتاحة: |
http://www.molecularbrain.com/content/8/1/15Test |
| حقوق: |
Copyright 2015 Gu et al.; licensee BioMed Central. |
| رقم الانضمام: |
edsbas.420D0661 |
| قاعدة البيانات: |
BASE |
