Functional Modulation of Nav1.2 Voltage-Gated Sodium Channels Induced by Escitalopram

• Published in: Biological & pharmaceutical bulletin 2018/09/01, Vol.41(9), pp.1471-1474
• Main Authors: Nakatani, Yoshihiko, Amano, Taku
• Format: Article
• Language: English
• Subjects: escitalopram; HEK293; Nav1.2 voltage-gated sodium channels (VGSCs)
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b18-00214

Escitalopram, a selective serotonin reuptake inhibitor (SSRI), may induce seizures, particularly in epileptic patients. In this study, we investigated the effect of escitalopram in Nav1.2 voltage-gated sodium channels (VGSCs) transfected HEK293 cells. Nav1.2 VGSCs current decreased by approximately 50.7±8.3% under treatment with 100 µM escitalopram. The IC50 of escitalopram against Nav1.2 VGSCs was 114.17 µM. Moreover, the treatment with 100 µM escitalopram changed the voltage-dependence of inactivation and the voltage at half-maximal inactivation shifted significantly from −50.3±3.7 to −56.7±6.0 mV toward negative potential under treatment with 100 µM escitalopram. Surprisingly, the treatment with 100 µM escitalopram also changed the voltage-dependence of activation and the voltage at half-maximal activation shifted significantly from −13.8±4.6 to −21.5±3.9 mV toward negative potential under treatment with 100 µM escitalopram. These findings suggested that escitalopram might be able to inhibit Nav1.2 VGSCs current and affects both activation and inactivation states of Nav1.2 VGSCs.