Objective Melittin （MEL） is a major component of bee venom and can produce both persistent spontaneous nociception and pain hypersensitivity when injected subcutaneously in the periphery. The present study aimed to ...Objective Melittin （MEL） is a major component of bee venom and can produce both persistent spontaneous nociception and pain hypersensitivity when injected subcutaneously in the periphery. The present study aimed to examine the roles of transient receptor potential canonical （TRPC） channels in mediation of MEL-indueed activation of primary nociceptive cells. Methods Whole-cell patch-clamp and laser scanning confocal calcium detection were used to evalu- ate the effects of SKF-96365, a TRPC inhibitor, applied on the acutely isolated dorsal root ganglion （DRG） cells of rat, on MEL-induced increase in intracellular calcium concentration （[Ca2＋]i） and inward current. Results Under voltage- clamp mode, 43.9% （40/91） DRG cells were evoked to give rise to the inward current by 2 pmol/L MEL, which could be significantly suppressed by 3 doses of SKF-96365 （1, 5 and 10μmol/L） in a dose-dependent manner. Of the other 210 cells, 67.6% responded to MEL with an intracellular Ca2＋ rise, as revealed by confocal calcium imaging. Of these MEL- sensitive cells, 46.5% （66/142） were suppressed by the highest dose of SKF-96365. Conclusion MEL-induced activation of small to medium-sized DRG cells can be suppressed by SKF-96365, suggesting the involvement of TRPC channels in the mediation of MEL-induced activation of primary nociceptive cells.展开更多
基金supported by the National Natural Science Foundation of China (No. 30670692, 30770668)the Natural Science Foundation of Beijing, China (No. KZ200510025016)
基金supported by thegrants from National Natural Science Foundation of China (No. 30770668, 81070899)Beijing Natural Science Foundation (No. 7102019)Natural Science Foundation of Education Committee of Beijing Municipality, China (No. KM201010025005)
文摘Objective Melittin （MEL） is a major component of bee venom and can produce both persistent spontaneous nociception and pain hypersensitivity when injected subcutaneously in the periphery. The present study aimed to examine the roles of transient receptor potential canonical （TRPC） channels in mediation of MEL-indueed activation of primary nociceptive cells. Methods Whole-cell patch-clamp and laser scanning confocal calcium detection were used to evalu- ate the effects of SKF-96365, a TRPC inhibitor, applied on the acutely isolated dorsal root ganglion （DRG） cells of rat, on MEL-induced increase in intracellular calcium concentration （[Ca2＋]i） and inward current. Results Under voltage- clamp mode, 43.9% （40/91） DRG cells were evoked to give rise to the inward current by 2 pmol/L MEL, which could be significantly suppressed by 3 doses of SKF-96365 （1, 5 and 10μmol/L） in a dose-dependent manner. Of the other 210 cells, 67.6% responded to MEL with an intracellular Ca2＋ rise, as revealed by confocal calcium imaging. Of these MEL- sensitive cells, 46.5% （66/142） were suppressed by the highest dose of SKF-96365. Conclusion MEL-induced activation of small to medium-sized DRG cells can be suppressed by SKF-96365, suggesting the involvement of TRPC channels in the mediation of MEL-induced activation of primary nociceptive cells.
