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Inhibition of sodium channels in acutely isolated hippocampal neurons by scorpion venom heat resistant protein

Zhang Xiaoyun, Wang Yue, Zhang Jian, Wang Jingyu, Zhao Jie, Zhang Wanqin, Li Shao

Department of Physiology, Institute of Brain Disorder, Dalian Medical University.Dalian 116027,Liaoning

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 （IC50） was （0.0034±0.0004） #mu#g/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 #mu#g/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 #mu#g/mL SVHRP. In the presence of 0.1 #mu#g/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.

Key words: scorpion venom heat resistant protein;whole-cell patch-clamp;sodium channels;hippocampal neuron

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Citing This Article：

Zhang Xiaoyun, Wang Yue, Zhang Jian, Wang Jingyu, Zhao Jie, Zhang Wanqin, Li Shao. Inhibition of sodium channels in acutely isolated hippocampal neurons by scorpion venom heat resistant protein. Acta Physiol Sin 2007; 59 (3): 278-284 (in Chinese with English abstract).