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[Inhibition of Jingzhaotoxin-V on Kv4.3 channel].
Sheng Li Xue Bao. 2010 Jun 25; 62(3):255-60.SL

Abstract

Kv4.3 channel is present in many mammalian tissues, predominantly in the heart and central nervous system. Its currents are transient, characterized by rapid activation and inactivation. In the hearts of most mammals, it is responsible for repolarization of the action potential of ventricular myocytes and is important in the regulation of the heart rate. Because of its central role in this important physiological process, Kv4.3 channel is a promising target for anti-arrhythmic drug development. Jingzhaotoxin-V (JZTX-V) is a novel peptide neurotoxin isolated from the venom of the spider Chilobrachys jingzhao. Whole-cell patch clamp recording showed that it partly blocked the transient outward potassium channels in dorsal root ganglion neurons of adult rats with an IC(50) 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 and separated 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 was used to characterize the action of JZTX-V on Kv4.3 channels expressed in Xenopus laevis oocytes. As a result, JZTX-V displayed fast kinetics of inhibition and recovery from inactivation. Furthermore, it could inhibit Kv4.3 channel current in a time- and concentration-dependent manner with an IC(50) value of 425.1 nmol/L. The application of JZTX-V affected the activation and inactivation characteristics of Kv4.3 channel and caused a shift of the current-voltage relationship curve and the steady-state inactivation curve to depolarizing direction by approximately 29 mV and 10 mV, respectively. So we deduced that JZTX-V is a gating modifier toxin of Kv4.3 channel. Present findings should be helpful to develop JZTX-V into a molecular probe and drug candidate targeting to Kv4.3 channel in the myocardium.

Authors+Show Affiliations

Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, Hunan Normal University, Changsha, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

chi

PubMed ID

20571743

Citation

Cai, Li-Jun, et al. "[Inhibition of Jingzhaotoxin-V On Kv4.3 Channel]." Sheng Li Xue Bao : [Acta Physiologica Sinica], vol. 62, no. 3, 2010, pp. 255-60.
Cai LJ, Xu DH, Luo J, et al. [Inhibition of Jingzhaotoxin-V on Kv4.3 channel]. Sheng Li Xue Bao. 2010;62(3):255-60.
Cai, L. J., Xu, D. H., Luo, J., Chen, R. Z., Chi, Y. P., Zeng, X. Z., Wang, X. C., & Liang, S. P. (2010). [Inhibition of Jingzhaotoxin-V on Kv4.3 channel]. Sheng Li Xue Bao : [Acta Physiologica Sinica], 62(3), 255-60.
Cai LJ, et al. [Inhibition of Jingzhaotoxin-V On Kv4.3 Channel]. Sheng Li Xue Bao. 2010 Jun 25;62(3):255-60. PubMed PMID: 20571743.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Inhibition of Jingzhaotoxin-V on Kv4.3 channel]. AU - Cai,Li-Jun, AU - Xu,De-Hong, AU - Luo,Ji, AU - Chen,Ren-Zhong, AU - Chi,Yu-Peng, AU - Zeng,Xiong-Zhi, AU - Wang,Xian-Chun, AU - Liang,Song-Ping, PY - 2010/6/24/entrez PY - 2010/6/24/pubmed PY - 2015/4/22/medline SP - 255 EP - 60 JF - Sheng li xue bao : [Acta physiologica Sinica] JO - Sheng Li Xue Bao VL - 62 IS - 3 N2 - Kv4.3 channel is present in many mammalian tissues, predominantly in the heart and central nervous system. Its currents are transient, characterized by rapid activation and inactivation. In the hearts of most mammals, it is responsible for repolarization of the action potential of ventricular myocytes and is important in the regulation of the heart rate. Because of its central role in this important physiological process, Kv4.3 channel is a promising target for anti-arrhythmic drug development. Jingzhaotoxin-V (JZTX-V) is a novel peptide neurotoxin isolated from the venom of the spider Chilobrachys jingzhao. Whole-cell patch clamp recording showed that it partly blocked the transient outward potassium channels in dorsal root ganglion neurons of adult rats with an IC(50) 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 and separated 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 was used to characterize the action of JZTX-V on Kv4.3 channels expressed in Xenopus laevis oocytes. As a result, JZTX-V displayed fast kinetics of inhibition and recovery from inactivation. Furthermore, it could inhibit Kv4.3 channel current in a time- and concentration-dependent manner with an IC(50) value of 425.1 nmol/L. The application of JZTX-V affected the activation and inactivation characteristics of Kv4.3 channel and caused a shift of the current-voltage relationship curve and the steady-state inactivation curve to depolarizing direction by approximately 29 mV and 10 mV, respectively. So we deduced that JZTX-V is a gating modifier toxin of Kv4.3 channel. Present findings should be helpful to develop JZTX-V into a molecular probe and drug candidate targeting to Kv4.3 channel in the myocardium. SN - 0371-0874 UR - https://www.unboundmedicine.com/medline/citation/20571743/[Inhibition_of_Jingzhaotoxin_V_on_Kv4_3_channel]_ L2 - http://www.actaps.com.cn/qikan/manage/wenzhang/2010-3-10.pdf DB - PRIME DP - Unbound Medicine ER -