Modulation of KV7.1 by NaVβ1 Subunit

Abstract

Several small proteins, referred to as “β-subunits”, have been shown to modulate the activity of potassium-selective, voltage-gated (KV) channels, rendering K+-conductance with different voltage dependence and kinetics. The physiological role of these interactions has been identified in some case. For instance, the interaction of KV7.1 and KCNE1 produces the cardiac K+-current known as IKS, which has a slower kinetics and negatively shifted voltage dependence for activation with respect to KV7.1 alone. In contrast, KCNE3 renders a channel that is open at physiological potentials. This characteristic of KV7.1 makes it into a versatile “α-subunit” with activity that can be physiologically customized by β-subunits. Recent studies have shown that NaVβ1, which is regarded as a β-subunit of sodium-selective, voltage-gated (NaV) channels, can modulate the activity of several KV channels. Since both KV7.1 and NaVβ1 are expressed in the hippocampus and cerebellum of mice, we wonder whether these two proteins could functionally interact. Thus, we recorded K+-currents from Xenopus oocytes co-expressing KV7.1 and NaVβ1 using the Cut-open Oocyte Voltage Clamp technique. We found that the expression of NaVβ1 caused KV7.1 to display a slow inactivating-like behavior, decreasing the K+-conductance over 20% after depolarization to −10 mV and above. Further, the deactivation rate of the K+-current decreased, displaying at least three phases, namely, a partial recovery from inactivation, a fast deactivating phase, and a slower deactivating phase. The rate of the initial fast deactivation was similar to the deactivating rate of the KV7.1 expressed alone. In contrast, the rate of the slow deactivation was 2-fold slower than the rate of deactivation of KV7.1 alone. Furthermore, our results indicate that NaVβ1 was able to modulate the voltage dependence for activation KV7.1 showing an apparent displacement of −20 mV. The physiological significance of this interaction is yet to be determined.