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[Inhibition of Jingzhaotoxin-V on Kv4.3 channel.] [Ariticle in Chinese]

CAI Li-Jun, XU De-Hong, LUO Ji, CHEN Ren-Zhong, CHI Yu-Peng, ZENG Xiong-Zhi^*, WANG Xian-Chun, LIANG Song-Ping

Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, Hunan Normal University, Changsha 410081, China

Abstract

Kv4.3 channel is present in many mammalian tissues, predominantly in the heart and central nervous system. Its currents aretransient, characterized by rapid activation and inactivation. In the hearts of most mammals, it is responsible for repolarization of theaction potential of ventricular myocytes and is important in the regulation of the heart rate. Because of its central role in this importantphysiological process, Kv4.3 channel is a promising target for anti-arrhythmic drug development. Jingzhaotoxin-V (JZTX-V) is a novelpeptide neurotoxin isolated from the venom of the spider Chilobrachys jingzhao. Whole-cell patch clamp recording showed that itpartly blocked the transient outward potassium channels in dorsal root ganglion neurons of adult rats with an IC50 value of 52.3 nmol/L.To investigate the effect of JZTX-V on Kv4.3 channel, JZTX-V was synthesized using the solid-phase chemical synthesis andseparated by reverse phase high performance liquid chromatography (HPLC). The purity was tested by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MOLDI-TOF mass spectrometry). Two-electrode voltage-clamp technique wasused to characterize the action of JZTX-V on Kv4.3 channels expressed in Xenopus laevis oocytes. As a result, JZTX-V displayed fastkinetics of inhibition and recovery from inactivation. Furthermore, it could inhibit Kv4.3 channel current in a time- and concentrationdependentmanner with an IC50 value of 425.1 nmol/L. The application of JZTX-V affected the activation and inactivation characteristicsof Kv4.3 channel and caused a shift of the current-voltage relationship curve and the steady-state inactivation curve to depolar izing direction by approximately 29 mV and 10 mV, respectively. So we deduced that JZTX-V is a gating modifier toxin of Kv4.3channel. Present findings should be helpful to develop JZTX-V into a molecular probe and drug candidate targeting to Kv4.3 channelin the myocardium.

Key words: Jingzhaotoxin-V; Kv4.3 channel; voltage clamp techniques; Xenopus laevis

Received: 2010-03-01　　Accepted: 2010-04-15

Corresponding author: 曾雄智　　E-mail: xiongzhizeng@yahoo.com.cn

Citing This Article：

CAI Li-Jun, XU De-Hong, LUO Ji, CHEN Ren-Zhong, CHI Yu-Peng, ZENG Xiong-Zhi, WANG Xian-Chun, LIANG Song-Ping. [Inhibition of Jingzhaotoxin-V on Kv4.3 channel.] [Ariticle in Chinese] . Acta Physiol Sin 2010; 62 (3): 255-260 (in Chinese with English abstract).