Auxiliary KCNE subunits modulate both homotetrameric Kv2.1 and heterotetrameric Kv2.1/Kv6.4 channels

Sci Rep. 2015 Aug 5:5:12813. doi: 10.1038/srep12813.

Abstract

The diversity of the voltage-gated K(+) (Kv) channel subfamily Kv2 is increased by interactions with auxiliary β-subunits and by assembly with members of the modulatory so-called silent Kv subfamilies (Kv5-Kv6 and Kv8-Kv9). However, it has not yet been investigated whether these two types of modulating subunits can associate within and modify a single channel complex simultaneously. Here, we demonstrate that the transmembrane β-subunit KCNE5 modifies the Kv2.1/Kv6.4 current extensively, whereas KCNE2 and KCNE4 only exert minor effects. Co-expression of KCNE5 with Kv2.1 and Kv6.4 did not alter the Kv2.1/Kv6.4 current density but modulated the biophysical properties significantly; KCNE5 accelerated the activation, slowed the deactivation and steepened the slope of the voltage-dependence of the Kv2.1/Kv6.4 inactivation by accelerating recovery of the closed-state inactivation. In contrast, KCNE5 reduced the current density ~2-fold without affecting the biophysical properties of Kv2.1 homotetramers. Co-localization of Kv2.1, Kv6.4 and KCNE5 was demonstrated with immunocytochemistry and formation of Kv2.1/Kv6.4/KCNE5 and Kv2.1/KCNE5 complexes was confirmed by Fluorescence Resonance Energy Transfer experiments performed in HEK293 cells. These results suggest that a triple complex consisting of Kv2.1, Kv6.4 and KCNE5 subunits can be formed. In vivo, formation of such tripartite Kv2.1/Kv6.4/KCNE5 channel complexes might contribute to tissue-specific fine-tuning of excitability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • HEK293 Cells
  • Humans
  • Membrane Potentials
  • Mice
  • Potassium Channels, Voltage-Gated / metabolism*
  • Potassium Channels, Voltage-Gated / physiology
  • Protein Structure, Quaternary
  • Protein Subunits / physiology
  • Protein Transport
  • Shab Potassium Channels / metabolism*

Substances

  • KCNB1 protein, human
  • KCNE1 protein, human
  • KCNE2 protein, human
  • KCNE3 protein, human
  • KCNE4 protein, mouse
  • KCNE5 protein, human
  • KCNG3 protein, human
  • Potassium Channels, Voltage-Gated
  • Protein Subunits
  • Shab Potassium Channels