2. Academic Validation
  3. Characteristics of hERG and hNav1.5 channel blockade by sulcardine sulfate, a novel anti-arrhythmic compound

Characteristics of hERG and hNav1.5 channel blockade by sulcardine sulfate, a novel anti-arrhythmic compound

  • Eur J Pharmacol. 2019 Feb 5:844:130-138. doi: 10.1016/j.ejphar.2018.12.009.
Weihai Chen 1,  Lu Gan 2,  Yiping Wang 3
Affiliations

Affiliations

  • 1 Key Laboratory of Cognition and Personality (Southwest University), Ministry of Education; Faculty of Psychology, Southwest University, Chongqing, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. Electronic address: whchen@swu.edu.cn.
  • 2 Key Laboratory of Cognition and Personality (Southwest University), Ministry of Education; Faculty of Psychology, Southwest University, Chongqing, China.
  • 3 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
PMID: 30529471 DOI: 10.1016/j.ejphar.2018.12.009
Abstract

Sulcardine sulfate (sulcardine) is a novel anti-arrhythmic compound, which blocks multiple channels and was shown to be safe and tolerated in clinical trials. The aim of the present study was to investigate the electrophysiological characteristics of sulcardine on the hERG and hNav1.5 channels. The hERG and hNav1.5 channels were heterologously stably expressed in human embryonic kidney 293 cells, and the effects of sulcardine on the hERG and hNav1.5 channels were recorded using the standard whole-cell patch-clamp technique. Sulcardine inhibited hERG channels in a concentration-dependent and reversible manner (IC50 = 94.3 μM). In addition, sulcardine shifted the activation curve of hERG channels to more negative potentials. The relative block of sulcardine on hERG channels was close to zero at the time point corresponding to channel opening, which was achieved by applying a depolarizing voltage, and quickly increased afterward. Sulcardine inhibited hNav1.5 channels in a concentration-dependent and reversible manner (IC50 = 15.0 μM) and shifted the inactivation curve of hNav1.5 channels to more negative potentials. The blockade of sulcardine on hNav1.5 channels was use-dependent. In conclusion, sulcardine is a potent hNav1.5 channel blocker with a mild inhibitory effect on hERG channels and preferentially binds to both hERG and hNav1.5 channels in the open and inactivated states rather than in the resting state.

Keywords

Arrhythmia; Human ether-a-go-go-related gene (hERG); Sulcardine sulfate; The cardiac sodium channels (hNav1.5); torsade de pointes arrhythmia.

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