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

作者：Radicke S^*; Riedel T; Cotella D; Turnow K; Ravens U; Schaefer M; Wettwer E

来源：Journal of Molecular and Cellular Cardiology, 2013, 56: 8-18.

DOI：10.1016/j.yjmcc.2012.12.017

• Temperature dependence
• Transient outward current
• Kv4.3 channel
• beta-subunits
• Markov model

In human atrial myocytes the transient outward current I-to develops a conspicuous faster inactivation with increasing temperatures. Since beta-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 a-subunit Kv43 but also by its interaction with accessory beta-subunits. We therefore studied the influence of the transmembrane beta-subunits KCNE1, KCNE2 and DPP6 on Kv43/KChIP2 channels in CHO cells at room temperature and at physiological temperature. Exposure to 37 degrees C caused a significant acceleration of the channel kinetics, whereas current densities and voltage dependences remained unaltered at 37 degrees C compared to 23 degrees C. However, Kv4.3/KChIP2 channels without transmembrane beta-subunits showed the strongest temperature sensitivity with considerably increased rates of activation and inactivation at 37 degrees C. KCNE2 significantly slowed the current kinetics at 37 degrees C compared to Kv43/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 degrees C were diminished at physiological temperature, thus at 37 degrees C current kinetics became remarkably similar for channel complexes Kv43/KChIP2 with and without DPP6 isoforms. A Markov state model was developed on the basis of experimental measurements to simulate the influence of beta-subunits on Kv43 channel complex at both temperatures. In conclusion, the remarkably fast kinetics of the native I-to at 37 degrees C could be reproduced by co-expressing Kv43, KChIP2, KCNE2 and DPP6 in CHO cells, whereas the high temperature sensitivity of human I-to could be not mimicked.

• 出版日期2013-3