BmP02,a peptide with 28 residues from the Chinese scorpion ButhusmartensiKarsch,hasbeen reported to inhibit the transient outward potassium currents(Ito??)in rat ventricular muscle in vitro(citation?).However,it still remains unclear if BmP02 modulates the Kv4.2 channel postulated(???)to be a contributor to Ito currents.The present study investigates the modulatory effects of BmP02 on Kv4.2 kinetics and its underlying molecular mechanism.The electrophysiological recordings showed that inactivation of Kv4.2 channels overexpressed in HEK 293T cells was modulatedby BmP02 in a distinct way while the peak current and activation of Kv4.2 were not affected.Though the voltage-dependence of Kv4.2 inactivation was hardly changed by BmP02,the inactivation was significantly delayed by this peptide in a dose-response manner with IC50 of~850 nM.In contrast,the recovery of channel activity from Kv4.2 inactivation was accelerated by the peptide.Besides these,the deactivation of Kv4.2 was slowed after the application of BmP02.The mutagenesis combined with computational modelling identified that K347 and K353 in the turret motif of the Kv4.2 pore region are the key residues to interact with BmP02 through electrostatic force.These findings reveals a novel interaction between Kv4.2 channel and its peptidylmodulator and provides valuable insight intohow a highly-selective Kv4.2 modulator can be developed.