کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5823505 | 1118335 | 2013 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Modulation of A-type K+ channels by the short-chain cobrotoxin through the protein kinase C-delta isoform decreases membrane excitability in dorsal root ganglion neurons
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
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چکیده انگلیسی
A-type K+ channels are crucial in controlling neuronal excitability, and their regulation in sensory neurons may alter pain sensation. In this study, we identified the functional role of cobrotoxin, the short-chain α-neurotoxin isolated from Naja atra venom, which acts in the regulation of the transient A-type K+ currents (IA) and membrane excitability in dorsal root ganglion (DRG) neurons via the activation of the muscarinic M3 receptor (M3R). Our results showed that cobrotoxin increased IA in a concentration-dependent manner, whereas the sustained delayed rectifier K+ currents (IDR) were not affected. Cobrotoxin did not affect the activation of IA markedly, however, it shifted the inactivation curve significantly in the depolarizing direction. The cobrotoxin-induced IA response was blocked by the M3R-selective antagonists DAU-5884 and 4-DAMP. An siRNA targeting the M3R in small DRG neurons abolished the cobrotoxin-induced IA increase. In addition, dialysis of the cells with the novel protein kinase C-delta isoform (PKC-δ) inhibitor δv1-1 or an siRNA targeting PKC-δ abolished the cobrotoxin-induced IA response, whereas inhibition of PKA or classic PKC activity elicited no such effects. Moreover, we observed a significant decrease in the firing rate of the neuronal action potential induced by M3R activation. Pretreatment of the cells with 4-aminopyridine, a selective blocker of IA, abolished this effect. Taken together, these results suggest that the short-chain cobrotoxin selectively enhances IA via a novel PKC-δ-dependent pathway. This effect occurred via the activation of M3R and might contribute to its neuronal hypoexcitability in small DRG neurons.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 85, Issue 9, 1 May 2013, Pages 1352-1362
Journal: Biochemical Pharmacology - Volume 85, Issue 9, 1 May 2013, Pages 1352-1362
نویسندگان
Qiang Guo, You-Jing Jiang, Hong Jin, Xing-Hong Jiang, Bo Gu, Yi-Ming Zhang, Jian-Gong Wang, Zheng-Hong Qin, Jin Tao,