Objective The rapid inactivation of Kv1.4 channel was assumed to be mediated through the "ball and chain" model which was perfectly suitable for ShB channel.However, some investigations have suggested that inactivation properties of Kv1.4 channel are different from ShB channel in that it has not an apparent chain structure.There are two highly charged regions (carrying charges opposite to each other) in the "chain" region of Kv 1.4 channel, one is rich of positive charges (residues 83-98: segment A) and the other rich of negative charges (residues 123-137: segment B).The objective of this study is to examine the electrostatic interactions between these two regions and explain the difference in inactivation property between Kv 1.4 and ShB channels.Methods We construct a series of mutants by standard molecular method, including neutralizing or deleting the positively charged segment A; replacing the positively charged segment A with negatively charged segment B (and vice versa); exchanging positively charged segment A with negatively charged segment B.The inactivation properties of these mutants were examined by voltage-clamp experiments.Results (1) Neutralizing or deleting positively charged segment A slowed the inactivation rate of Kv1.4 channel; (2) The mutants, which carried both positive or negative charges at these two regions, inactivated much more slowly compared with Kvl.4WT; (3) Exchanging these two segments with each other did not affect the inactivation rate.Conclusion All these results indicate that there are electrostatic attractions between positively charged segment A and negatively charged segment B and the electrostatic interaction between them accelerates the inactivation rate of Kv 1.4 channel.