Molecular Dynamics Study of Protein-Mediated Electroporation of Kv Channels Induced by nsPEFs: Advantages of Bipolar Pulses.

Nanosecond pulsed electric fields (nsPEFs) can induce protein-mediated electroporation (PMEP) in voltage-gated ion channels. However, their effects on the tetrameric structure of voltage-gated potassium (Kv) channels remain unexplored. Our study pioneered the molecular dynamics (MD) investigation of the open-state (O) Kv channel to understand the effects of PMEP under unipolar and bipolar pulses (UP and BP). Our findings revealed that BP induces pore formation more effectively than UP. Additionally, the frequency of pore formation shows a more consistent decline with increased pulse interval under BP. We further examined three other distinct functional states─intermediate (C*), inactivated (I), and resting closed (C)─of Kv channels under BP. SF pores formed exclusively in the O state, while complex pores formed only in the O and C states. In conclusion, our study highlights BP's role in enhancing pore formation and specificity, offering insights into Kv channel PMEP and its therapeutic potential.