Electrostatic interactions during Kv1.2 N-type inactivation: Random-walk simulation

N-type inactivation of the Kv1.2 voltage-gated potassium channel is a process in which the N-terminal of the protein (its first 20 amino acids) binds to the open-channel surface, extends and occludes its pore. This process has been experimentally studied in both intact and ShBΔ6-46 channels in which the inactivating peptides are supplied in the bath solution. In this work we provide a qualitative description of N-type inactivation by simulating the random walk of charged inactivating peptides in the electrostatic field that originates from the charges present in the channel and in the cellular membrane. Our results give a deeper insight into the previously reported influence of electrostatics on the rate of N-type inactivation of ShBΔ6-46. We also show how the enchaining of the peptides, i.e., considering the intact form of the channel, influences the N-type inactivation with different charges of those peptides.