Differential modulation of Kv1 channel-mediated currents by co-expression of Kvβ3 subunit in a mammalian cell-line

Abstract

The effect of Kvβ3 subunit co-expression on currents mediated by the Shaker-related channels Kv1.1 to Kv1.6 in Chinese hamster ovary (CHO) cells was studied with patch-clamp techniques. In the presence of Kvβ3, differences in the voltage dependence of activation for Kv1.1, Kv1.3, Kv1.5 and Kv1.6 were detected, but not for Kv1.2- and Kv1.4-mediated currents. Co-expression of Kvβ3 did not cause a significant increase in current density for any of the tested channels. In contrast to previous studies in the Xenopus oocyte expression system, Kvβ3 confered a rapid inactivation to all except Kv1.3 channels. Also, Kv1.6 channels that possess an N-type inactivation prevention (NIP) domain for Kvβ1.1, inactivated rapidly when co-expressed with Kvβ3. Onset and recovery kinetics of channel inactivation distinctly differed for the various Kv1α/ Kvβ3 subunit combinations investigated in this study. The results indicate that the choice of expression system may critically determine Kvβ3 inactivating activity. This suggests that the presence of an inactivating domain and a receptor in the channel pore, although necessary, may not be sufficient for an effective rapid N-type inactivation of Kv1 channels in heterologous expression systems.