Saito Shigeru, Radwan Inas A M, Nishikawa Koichi, Obata Hideaki, Okamoto Tomonori, Kanno Toshio, Goto Fumio
Department of Anesthesiology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Anesth Analg. 2004 Mar;98(3):841-5, table of contents. doi: 10.1213/01.ane.0000099718.51681.55.
Neurotoxicity of local anesthetics has been reported for both matured and growing neurons. In the present study, we examined if tetracaine increases Ca(2+) concentration during growth cone collapse. Intracellular Ca(2+) concentration was measured by fura 2/AM after exposure to tetracaine. Tetracaine (1-2 mM) induced increases in intra-growth cone Ca(2+) concentration (P < 0.01). The Ca(2+) hot spot was expanded into the neurite from the periphery towards the cell body. When tetracaine was applied to growth cones in Ca(2+) free media, the increase was minor. However, tetracaine induced growth cone collapse even in the culture media, which did not contain Ca(2+). Ni(2+) (100 microM; a general Ca(2+) channel inhibitor) and BAPTA-AM (5 microM; intracellular Ca(2+) chelator) could not inhibit growth cone collapse induced by 1-2 mM tetracaine. Tetracaine (>1 mM) induces collapse and Ca(2+) increase at growth cones simultaneously; however, these two phenomena might be provoked independently.
Tetracaine induced intracellular Ca(2+) increases and growth cone collapse in dorsal root ganglion neurons. The Ca(2+) hot spot in the growth cone expanded into the neurite from periphery towards the cell body.
已有报道称局部麻醉药对成熟神经元和生长中的神经元均有神经毒性。在本研究中,我们检测了丁卡因在生长锥塌陷过程中是否会增加钙离子浓度。暴露于丁卡因后,用fura 2/AM测量细胞内钙离子浓度。丁卡因(1-2 mM)可诱导生长锥内钙离子浓度升高(P < 0.01)。钙离子热点从周边向细胞体方向扩展到神经突。当在无钙培养基中对生长锥施加丁卡因时,升高幅度较小。然而,即使在不含钙离子的培养基中,丁卡因也能诱导生长锥塌陷。镍离子(100 microM;一种通用的钙离子通道抑制剂)和BAPTA-AM(5 microM;细胞内钙离子螯合剂)不能抑制1-2 mM丁卡因诱导的生长锥塌陷。丁卡因(>1 mM)可同时诱导生长锥塌陷和钙离子浓度升高;然而,这两种现象可能是独立引发的。
丁卡因可诱导背根神经节神经元细胞内钙离子浓度升高和生长锥塌陷。生长锥内的钙离子热点从周边向细胞体方向扩展到神经突。