Regulatory role of the extreme C‐terminal end of the S6 inner helix in C‐terminal‐truncated Kv1.2 channel activation

The transmembrane part of the S6 inner helix of the Kv1.2 potassium channel is a pivotal part in sustaining channel activity. However, the role of its extreme C-terminal end, which is located on the cytoplasmic side of the channel, is largely unknown. Here, we investigated the role of the extreme C-terminal end of the S6 inner helix (the HRET region) by constructing a series of C-terminal-truncated mutations related to this region in the C-terminal-truncated Kv1.2 channel. Mutations on Thr421 or Glu420 significantly altered the activation of the truncated channel. Mutations on Arg419 demonstrated that neutral or basic, but not acidic amino acid, is essential at the position for the truncated channel activation, and no functional channel was observed when the channel was truncated from His418. Hence, our results indicate that the extreme C-terminal end of the S6 inner helix plays an important regulatory role in the activation of the C-terminal-truncated Kv1.2 channel.