Low-concentration lidocaine rapidly inhibits axonal transport in cultured mouse dorsal root ganglion neurons

Background: Axonal transport plays a critical role in supplying materials f or a variety of neuronal functions such as morphogenetic plasticity, synapt ic transmission, and cell survival. In the current study, the authors inves tigated the effects of the analgesic agent lidocaine on axonal transport in neurites of cultured mouse dorsal root ganglion neurons. In relation to th eir effects, the effects of lidocaine on the growth rate of the neurite wer e also examined. Methods: Isolated mouse dorsal root ganglion cells were cultured for 48 li until full grow-th of neurites. Video-enhanced microscopy was used to obser ve particles transported within neurites and to measure the neurite growth during control conditions and in the presence of lidocaine. Results: Application of 30 mum lidocaine immediately reduced the number of particles transported In anterograde and retrograde axonal directions. Thes e effects were persistently observed during the application (26 min) and we re reversed by lidocaine washout. The inhibitory effect was dose-dependent at concentrations from 0.1 to 1,000 mum (IC50 = 10 mum). In Ca2+-free extra cellular medium, lidocaine failed to inhibit axonal transport. Calcium iono phore A23187 (0.1 tw) reduced axonal transport in both directions. The inhi bitory effects of lidocaine and A23187 were abrogated by 10 mum KN-62, a Ca 2+-calmodulin-dependent protein kinase II inhibitor. Application of such lo w-concentration lidocaine (30 mum) for 30 min reduced the growth rate of ne urites, and this effect was also blocked by KN-62. Conclusions: Low-concentration lidocaine rapidly inhibits axonal transport and neurite growth via activation of calmodulin-dependent protein kinase II .