Effects of SKF-96365, a TRPC inhibitor, on melittin-induced inward current and intracellular Ca2+ rise in primary sensory cells
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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-induced activation of primary nociceptive cells.
Whole-cell patch-clamp and laser scanning confocal calcium detection were used to evaluate 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.
Under voltageclamp mode, 43.9% (40/91) DRG cells were evoked to give rise to the inward current by 2 μmol/L MEL, which could be significantly suppressed by 3 doses of SKF-96365 (1, 5 and 10 μmol/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.
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.
Keywordsmelittin transient receptor potential canonical channel dorsal root ganglion patch-clamp technique calcium imaging
TRPC 通道阻断剂SKF-96365 对蜜蜂毒肽诱发初级感觉细胞内向电流和胞内钙增高的作用
蜜蜂毒肽是蜜蜂粗毒中的主要物质。 外周皮下注射蜜蜂毒肽可导致持续性自发痛和痛觉过敏。 本研究旨在研究瞬时受体电势C (transient receptor potential canonical, TRPC) 通道在蜜蜂毒肽诱致的初级感觉神经元活化中的介导作用。
电压钳记录的91个背根神经节细胞中, 蜜蜂毒肽可诱发43.9% (40/91)的细胞产生内向电流, 而不同浓度的SKF-96365 (1, 5, 10 μmol/L) 均明显抑制了背根神经节细胞的内向电流, 且呈剂量相关性。 应用激光共聚焦钙成像技术记录的210个背根神经节细胞中, 67.6% 的细胞对蜜蜂毒肽敏感, 产生胞内钙离子浓度的升高, 而SKF-96365能抑制这种胞内钙浓度的升高, 抑制率为46.5%。
关键词蜜蜂毒肽 瞬时受体电势C通道 背根神经节 膜片钳技术 激光共聚焦测钙
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- Li KC, Chen J. Altered pain-related behaviors and spinal neuronal responses produced by s.c. injection of melittin in rats. Neuroscience 2004, 126: 753–762.Google Scholar