Intracellular calcium increases in growth cones exposed to tetracaine.
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.


CONCLUSIONS
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.
Saito
Shigeru
S
Department of Anesthesiology, Gunma University Graduate School of Medicine, Maebashi, Japan. shigerus@showa.gunma-u.ac.jp
Radwan
Inas A M
IA
Nishikawa
Koichi
K
Obata
Hideaki
H
Okamoto
Tomonori
T
Kanno
Toshio
T
Goto
Fumio
F
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D002642:Chick Embryo; D003470:Culture Media; D005456:Fluorescent Dyes; D016257:Fura-2; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D016501:Neurites / Q000187:drug effects / Q000648:ultrastructure; D013748:Tetracaine / Q000494:pharmacology*
D000779:Anesthetics, Local; D002121:Calcium Channel Blockers; D002614:Chelating Agents; D003470:Culture Media; D005456:Fluorescent Dyes; D013748:Tetracaine; D002118:Calcium; D016257:Fura-2