Selectivity filter instability dominates the low intrinsic activity of the TWIK-1 K2P K⁺ channel.

ABSTRACT: Two-pore domain K⁺ (K2P) channels have many important physiological functions. However, the functional properties of the TWIK-1 (K2P1.1/KCNK1) K2P channel remain poorly characterized because heterologous expression of this ion channel yields only very low levels of functional activity. Several underlying reasons have been proposed, including TWIK-1 retention in intracellular organelles, inhibition by posttranslational sumoylation, a hydrophobic barrier within the pore, and a low open probability of the selectivity filter (SF) gate. By evaluating these potential mechanisms, we found that the latter dominates the low intrinsic functional activity of TWIK-1. Investigating this further, we observed that the low activity of the SF gate appears to arise from the inefficiency of

SUBMITTER: Nematian-Ardestani E 

PROVIDER: S-EPMC6956551 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature