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

Bin Wu  Yan Zhu  Jian Shi  Jie Tao  Yonghua Ji  
【摘要】: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(I_(to)) in rat ventricular muscle cells.However,it remains unclear whether BmP02 modulates the Kv4.2 channel,one of the main contributors to I_(to).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 HEK293 T cells was significantly delayed by BmP02 in a doseresponse manner with EC_(50) 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.

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