Lipid bilayer modification alters the gating properties and pharmacological sensitivity of voltage-gated sodium channel.
- Author:
Yan ZHU
1
;
Bin WU
1
;
Yi-Jun FENG
1
;
Jie TAO
2
;
Yong-Hua JI
3
Author Information
1. Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200444, China.
2. Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China. jietao_putuo@foxmail.com.
3. Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200444, China. yhji@staff.shu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Cell Line, Tumor;
Humans;
Lipid Bilayers;
chemistry;
Neuroblastoma;
Scorpion Venoms;
chemistry;
Sodium Channel Blockers;
chemistry;
Voltage-Gated Sodium Channels;
physiology
- From:
Acta Physiologica Sinica
2015;67(3):271-282
- CountryChina
- Language:English
-
Abstract:
Voltage-gated sodium channels (VGSCs) are widely distributed in most cells and tissues, performing many physiological functions. As one kind of membrane proteins in the lipid bilayer, whether lipid composition plays a role in the gating and pharmacological sensitivity of VGSCs still remains unknown. Through the application of sphingomyelinase D (SMaseD), the gating and pharmacological sensitivity of the endogenous VGSCs in neuroblastoma ND7-23 cell line to BmK I and BmK AS, two sodium channel-specific modulators from the venom of Buthus martensi Karsch (BmK), were assessed before and after lipid modification. The results showed that, in ND7-23 cells, SMaseD did not change the gating properties of VGSCs. However, SMaseD application altered the slope factor of activation with the treatment of 30 nmol/L BmK I, but caused no significant effects at 100 and 500 nmol/L BmK I. With low concentration of BmK I (30 and 100 nmol/L) treatment, the application of SMaseD exerted hyperpolarizing effects on both slow-inactivation and steady-state inactivation, and increased the recovery time constant, whereas total inactivation and recovery remained unaltered at 500 nmol/L BmK I. Meanwhile, SMaseD modulation hyperpolarized the voltage dependence of slow-inactivation at 0.1 nmol/L BmK AS and altered the slope factor of slow-inactivation at 10 nmol/L BmK AS, whereas other parameters remained unchanged. These results indicated a possibility that the lipid bilayer would disturb the pharmacological sensitivity of VGSCs for the first time, which might open a new way of developing new drugs for treating sodium channelopathies.
