Accessory subunits alter the temperature sensitivity of Kv4.3 channel complexes

J Mol Cell Cardiol. 2013 Mar;56:8-18. doi: 10.1016/j.yjmcc.2012.12.017. Epub 2013 Jan 3.


In human atrial myocytes the transient outward current I(to) develops a conspicuous faster inactivation with increasing temperatures. Since β-subunits are known to modulate I(to) current kinetics, we hypothesized that the temperature sensitivity of I(to) is not only determined by the property of the ion-passing α-subunit Kv4.3 but also by its interaction with accessory β-subunits. We therefore studied the influence of the transmembrane β-subunits KCNE1, KCNE2 and DPP6 on Kv4.3/KChIP2 channels in CHO cells at room temperature and at physiological temperature. Exposure to 37°C caused a significant acceleration of the channel kinetics, whereas current densities and voltage dependences remained unaltered at 37°C compared to 23°C. However, Kv4.3/KChIP2 channels without transmembrane β-subunits showed the strongest temperature sensitivity with considerably increased rates of activation and inactivation at 37°C. KCNE2 significantly slowed the current kinetics at 37°C compared to Kv4.3/KChIP2 channels, whereas KCNE1 did not influence the channel properties at both temperatures. Interestingly, the accelerating effects of DPP6 on current kinetics described at 23°C were diminished at physiological temperature, thus at 37°C current kinetics became remarkably similar for channel complexes Kv4.3/KChIP2 with and without DPP6 isoforms. A Markov state model was developed on the basis of experimental measurements to simulate the influence of β-subunits on Kv4.3 channel complex at both temperatures. In conclusion, the remarkably fast kinetics of the native I(to) at 37°C could be reproduced by co-expressing Kv4.3, KChIP2, KCNE2 and DPP6 in CHO cells, whereas the high temperature sensitivity of human I(to) could be not mimicked.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • CHO Cells
  • Cricetinae
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / physiology
  • Humans
  • Ion Channel Gating
  • Kinetics
  • Markov Chains
  • Models, Biological
  • Nerve Tissue Proteins / physiology
  • Patch-Clamp Techniques
  • Potassium Channels / physiology
  • Potassium Channels, Voltage-Gated / physiology
  • Protein Stability
  • Protein Subunits / physiology*
  • Shal Potassium Channels / metabolism*
  • Thermodynamics


  • KCNE1 protein, human
  • KCNE2 protein, human
  • Nerve Tissue Proteins
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Protein Subunits
  • Shal Potassium Channels
  • DPP6 protein, human
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases