Lipid bilayer modification alters the gating properties and pharmacological sensitivity of voltage-gated sodium channel / 生理学报
Acta Physiologica Sinica
; (6): 271-282, 2015.
Article
in En
| WPRIM
| ID: wpr-255948
Responsible library:
WPRO
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.
Full text:
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Index:
WPRIM
Main subject:
Physiology
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Scorpion Venoms
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Chemistry
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Sodium Channel Blockers
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Cell Line, Tumor
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Voltage-Gated Sodium Channels
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Lipid Bilayers
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Neuroblastoma
Type of study:
Diagnostic_studies
Limits:
Humans
Language:
En
Journal:
Acta Physiologica Sinica
Year:
2015
Type:
Article