부산대학교 도서관

It has been repeatedly proved that Nav1.8 tetrodotoxin (TTX)‐resistant sodium currents are expressed in peripheral sensory neurons where they play important role in nociception. There are very few publications that show the presence of TTX‐resistant sodium currents in central neurons. The aim of this study was to assess if functional Nav1.8 TTX‐resistant sodium currents are expressed in prefrontal cortex pyramidal neurons. All recordings were performed in the presence of TTX in the extracellular solution to block TTX‐sensitive sodium currents. The TTX‐resistant sodium current recorded in this study was mainly carried by the Nav1.8 sodium channel isoform because the Nav1.9 current was inhibited by the −65 mV holding potential that we used throughout the study. Moreover, the sodium current that we recorded was inhibited by treatment with the selective Nav1.8 inhibitor A‐803467. Confocal microscopy experiments confirmed the presence of the Nav1.8 α subunit in prefrontal cortex pyramidal neurons. Activation and steady state inactivation properties of TTX‐resistant sodium currents were also assessed in this study and they were similar to activation and inactivation properties of TTX‐resistant sodium currents expressed in dorsal root ganglia (DRG) neurons. Moreover, this study showed that carbamazepine (60 µM) inhibited the maximal amplitude of the TTX‐resistant sodium current. Furthermore, we found that carbamazepine shifts steady state inactivation curve of TTX‐resistant sodium currents toward hyperpolarization. This study suggests that the Nav1.8 TTX‐resistant sodium channel is expressed not only in DRG neurons, but also in cortical neurons and may be molecular target for antiepileptic drugs such as carbamazepine. [ABSTRACT FROM AUTHOR]