Inhibition of sodium channels in acutely isolated hippocampal neurons by scorpion venom heat resistant protein.
- Author:
Xiao-Yun ZHANG
1
;
Yue WANG
;
Jian ZHANG
;
Jing-Yu WANG
;
Jie ZHAO
;
Wan-Qin ZHANG
;
Shao LI
Author Information
1. Department of Physiology, Institute of Brain Disorder, Dalian Medical University, Dalian 116027, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Dose-Response Relationship, Drug;
Female;
Hippocampus;
drug effects;
physiology;
In Vitro Techniques;
Male;
Patch-Clamp Techniques;
Rats;
Rats, Sprague-Dawley;
Scorpion Venoms;
pharmacology;
Sodium Channel Blockers;
pharmacology;
Tetrodotoxin;
pharmacology
- From:
Acta Physiologica Sinica
2007;59(3):278-284
- CountryChina
- Language:Chinese
-
Abstract:
The effects of scorpion venom heat resistant protein (SVHRP) on sodium channel were studied in freshly isolated hippocampal neurons in rat using the whole-cell patch-clamp technique. The results indicated that tetrodotoxin-sensitive voltage-dependent sodium current in hippocampal neurons was inhibited by SVHRP in a dose-dependent manner. The half-inhibition concentration (IC(50)) was (0.0034+/-0.0004) microg/mL, Hill constant (n) was 0.4361+/-0.0318. After SVHRP application, a clear shift of the activation curve of Na(+) channel was shown towards more depolarized potential, resulting in channel opening at more positive membrane potentials. In the presence of 0.1 mug/mL SVHRP, the voltage for half-activation (V(1/2)) and the slope factor of the activation curve were (-23.96+/-0.41) mV and 3.73+/-0.08 (n=8, P<0.05) compared with the control recordings of (-34.38+/-0.62) mV and 4.52+/-0.52 (n=16), respectively. Averaged and normalized curve of steady-state inactivation of Na(+) channel was shifted towards negative potential after treatment of 0.1 and 0.01 mug/mL SVHRP. In the presence of 0.1 mug/mL SVHRP, the voltage for half-inactivation (V(1/2)) and the slope factor determined by a sigmoid fit of the inactivation curve were (-50.69+/-2.55) mV (n=8, P<0.01) and 5.49+/-0.72 (n=8, P<0.05) compared with the control recordings of (-32.60+/-1.52) mV and 6.73+/-0.51 (n=16), respectively. These results suggest that SVHRP blocks the voltage-dependent sodium currents and alters the sodium channel kinetics to decrease the excitability of neurons. This might be an interpretation for the antiepileptic effects of SVHRP.
