Modal behavior of the Kv1.1 channel conferred by the Kvβ1.1 subunit and its regulation by dephosphorylation of Kv1.1

Abstract.

Modulation of fast-inactivating voltage-gated K⁺ channels can produce plastic changes in neuronal signaling. Previously, we showed that the voltage-dependent K⁺ channel composed of brain Kv1.1 and Kvβ1.1 subunits (αβ channel) gives rise to a current that has a fast-inactivating and a sustained component; the proportion of the fast-inactivating component could be decreased by dephosphorylation of a basally phosphorylated Ser-446 on the α subunit. To account for our results we suggested a model that assumes a bimodal gating of the αβ channel. In this study, using single-channel analysis, we confirm this model. Two modes of gating were identified: (1) an inactivating mode characterized by low open probability and single openings early in the voltage step, and (2) a non-inactivating gating mode with bursts of openings. These two modes were non-randomly distributed, with spontaneous shifts between them. Each mode is characterized by a different set of open time constants (τ) and mean open times (t_o). The non-inactivating mode is similar to the gating mode of a homomultimeric α channel. The phosphorylation-deficient α_S446Aβ channel has the same two gating modes. Furthermore, alkaline phosphatase promoted the transition to the non-inactivating mode. This is the first report of modal behavior of a fast-inactivating K⁺ channel; furthermore, it substantiates the notion that direct phosphorylation is one mechanism that regulates the equilibrium between the two modes and thereby regulates the extent of macroscopic fast inactivation of a brain K⁺ channel.