2. Academic Validation
  3. BmP02 Atypically Delays Kv4.2 Inactivation: Implication for a Unique Interaction between Scorpion Toxin and Potassium Channel

BmP02 Atypically Delays Kv4.2 Inactivation: Implication for a Unique Interaction between Scorpion Toxin and Potassium Channel

  • Toxins (Basel). 2016 Sep 27;8(10):280. doi: 10.3390/toxins8100280.
Bin Wu 1,  Yan Zhu 2,  Jian Shi 3 4,  Jie Tao 5,  Yonghua Ji 6
Affiliations

Affiliations

  • 1 Lab of Neuropharmacology and Neurotoxicology, Shanghai University, Nanchen Road 333, Shanghai 200444, China. [email protected].
  • 2 Lab of Neuropharmacology and Neurotoxicology, Shanghai University, Nanchen Road 333, Shanghai 200444, China. [email protected].
  • 3 Lab of Neuropharmacology and Neurotoxicology, Shanghai University, Nanchen Road 333, Shanghai 200444, China. [email protected].
  • 4 Vascular Biology Research Centre, Institute of Cardiovascular and Cell Sciences, St. George's, University of London, Cranmer Terrace, London SW17 0RE, UK. [email protected].
  • 5 Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi road, Shanghai 200062, China. [email protected].
  • 6 Lab of Neuropharmacology and Neurotoxicology, Shanghai University, Nanchen Road 333, Shanghai 200444, China. [email protected].
PMID: 27690098 DOI: 10.3390/toxins8100280
Abstract

BmP02, a short-chain peptide with 28 residues from the venom of Chinese scorpion Buthus martensi Karsch, has been reported to inhibit the transient outward potassium currents (Ito) in rat ventricular muscle cells. However, it remains unclear whether BmP02 modulates the Kv4.2 channel, one of the main contributors to Ito. The present study investigated the effects of BmP02 on Kv4.2 kinetics and its underlying molecular mechanism. The electrophysiological recordings showed that the inactivation of Kv4.2 expressed in HEK293T cells was significantly delayed by BmP02 in a dose-response manner with EC50 of ~850 nM while the peak current, activation and voltage-dependent inactivation of Kv4.2 were not affected. Meanwhile, the recovery from inactivation of Kv4.2 was accelerated and the deactivation was slowed after the application of BmP02. The site-directed mutagenesis combined with computational modelling identified that K347 and K353, located in the turret motif of the Kv4.2, and E4/E5, D20/D21 in BmP02 are key residues to interact with BmP02 through electrostatic force. These findings not only reveal a novel interaction between Kv4.2 channel and its peptidyl modulator, but also provide valuable information for design of highly-selective Kv4.2 modulators.

Keywords

electrophysiology; interaction mode; scorpion toxin; voltage-gated potassium channels.

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