Neuroscience Bulletin

, Volume 28, Issue 3, pp 209–221

Pharmacological kinetics of BmK AS, a sodium channel site 4-specific modulator on Nav1.3

Authors

  • Zhi-Rui Liu
    • Laboratory of Neuropharmacology and NeurotoxicologyShanghai University
  • Jie Tao
    • Laboratory of Neuropharmacology and NeurotoxicologyShanghai University
  • Bang-Qian Dong
    • Laboratory of Neuropharmacology and NeurotoxicologyShanghai University
  • Gang Ding
    • Xinhua Translational Institute for Cancer Pain
  • Zhi-Jun Cheng
    • Xinhua Translational Institute for Cancer Pain
  • Hui-Qiong He
    • Laboratory of Neuropharmacology and NeurotoxicologyShanghai University
    • Laboratory of Neuropharmacology and NeurotoxicologyShanghai University
Original Article

DOI: 10.1007/s12264-012-1234-6

Cite this article as:
Liu, Z., Tao, J., Dong, B. et al. Neurosci. Bull. (2012) 28: 209. doi:10.1007/s12264-012-1234-6

Abstract

Objective

In this study, the pharmacological kinetics of Buthus martensi Karsch (BmK) AS, a specific modulator of voltage-gated sodium channel site 4, was investigated on Nav1.3 expressed in Xenopus oocytes.

Methods

Two-electrode voltage clamp was used to record the whole-cell sodium current.

Results

The peak currents of Nav1.3 were depressed by BmK AS over a wide range of concentrations (10, 100, and 500 nmol/L). Most remarkably, BmK AS at 100 nmol/L hyperpolarized the voltage-dependence and increased the voltage-sensitivity of steady-state activation/inactivation. In addition, BmK AS was capable of hyperpolarizing not only the fast inactivation but also the slow inactivation, with a greater preference for the latter. Moreover, BmK AS accelerated the time constant and increased the ratio of recovery in Nav1.3 at all concentrations.

Conclusion

This study provides direct evidence that BmK AS facilitates steady-state activation and inhibits slow inactivation by stabilizing both the closed and open states of the Nav1.3 channel, which might result from an integrative binding to two receptor sites on the voltage-gated sodium channels. These results may shed light on therapeutics against Nav1.3-targeted pathology.

Keywords

VGSC subtypeNav1.3VGSC site 4-specific modulatorBmK AS
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Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg 2012