Molecular Mechanism of Depolarization-Dependent Inactivation in W366F Mutant of Kv1.2

Hiroko X. Kondo, Norio Yoshida, Matsuyuki Shirota, Kengo Kinoshita

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Voltage-gated potassium channels play crucial roles in regulating membrane potential. They are activated by membrane depolarization, allowing the selective permeation of K + ions across the plasma membrane, and enter a nonconducting state after lasting depolarization, a process known as inactivation. Inactivation in voltage-activated potassium channels occurs through two distinct mechanisms, N-type and C-type inactivation. C-type inactivation is caused by conformational changes in the extracellular mouth of the channel, whereas N-type inactivation is elicited by changes in the cytoplasmic mouth of the protein. The W434F-mutated Shaker channel is known as a nonconducting mutant and is in a C-type inactivation state at a depolarizing membrane potential. To clarify the structural properties of C-type inactivated protein, we performed molecular dynamics simulations of the wild-type and W366F (corresponding to W434F in Shaker) mutant of the Kv1.2-2.1 chimera channel. The W366F mutant was in a nearly nonconducting state with a depolarizing voltage and recovered from inactivation with a reverse voltage. Our simulations and three-dimensional reference interaction site model analysis suggested that structural changes in the selectivity filter upon membrane depolarization trap K + ions around the inner mouth of the selectivity filter and prevent ion permeation. This pore restriction is involved in the molecular mechanism of C-type inactivation.

Original languageEnglish
Pages (from-to)10825-10833
Number of pages9
JournalJournal of Physical Chemistry B
Issue number48
Publication statusPublished - Dec 6 2018

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry


Dive into the research topics of 'Molecular Mechanism of Depolarization-Dependent Inactivation in W366F Mutant of Kv1.2'. Together they form a unique fingerprint.

Cite this