Department of Chemistry and Molecular Biology , University of Gothenburg , Gothenburg 412 96 , Sweden.
Department of Chemistry and Chemical Engineering , Chalmers University of Technology , Gothenburg 412 96 , Sweden.
ACS Chem Neurosci. 2018 Dec 19;9(12):2941-2947. doi: 10.1021/acschemneuro.8b00130. Epub 2018 Jul 19.
Single cell amperometry and intracellular vesicle impact electrochemical cytometry were used to examine whether lidocaine can regulate neurotransmitter release or storage for PC12 cells to explain the biphasic effects whereby it can protect neurons and improve cognitive outcome at low concentration, but can cause neurotoxicity at high concentration. We show that lidocaine affects the behavior of PC12 cell exocytosis in a concentration dependent way, which exactly corresponds to its biphasic effects. At a relatively high concentration, it shows a much narrower pore size and a longer-duration fusion pore with less monoamine released than control cells. However, at a relatively low concentration, the fusion pore is open even longer than at high concentration, and with more monoamine released than control cells. Furthermore, intracellular vesicle impact electrochemical cytometry was used to confirm that lidocaine did not change the catecholamine content of the vesicles. These data provide a mechanism for the observed biphasic effects of the drug and suggest that lidocaine influences exocytosis through multiple mechanisms.
单细胞安培法和细胞内囊泡冲击电化学细胞术用于研究利多卡因是否可以调节 PC12 细胞的神经递质释放或储存，以解释其在低浓度时具有保护神经元和改善认知功能的双相作用，而在高浓度时则会引起神经毒性的原因。我们的研究表明，利多卡因以浓度依赖的方式影响 PC12 细胞胞吐的行为，这与它的双相作用完全一致。在相对较高的浓度下，它显示出更小的孔径和更长的融合孔持续时间，与对照细胞相比释放的单胺类物质更少。然而，在相对较低的浓度下，融合孔的开放时间甚至比高浓度下还要长，并且与对照细胞相比释放出更多的单胺类物质。此外，细胞内囊泡冲击电化学细胞术被用于证实利多卡因并未改变囊泡中的儿茶酚胺含量。这些数据为观察到的药物双相作用提供了一种机制，并表明利多卡因通过多种机制影响胞吐作用。
