Fast inactivation of a brain K⁺ channel composed of K(v)1.1 and K(v)β1.1 subunits modulated by G protein βγ subunits

Modulation of A-type voltage-gated K⁺ channels can produce plastic changes in neuronal signaling. It was shown that the delayed-rectifier K(v)1.1 channel can be converted to A-type upon association with K(v)β1.1 subunits; the conversion is only partial and is modulated by phosphorylation and microfilaments. Here we show that, in Xenopus oocytes, expression of Gβ₁γ₂ subunits concomitantly with the channel (composed of K(v)1.1 and K(v)β1.1 subunits), but not after the channel's expression in the plasma membrane, increases the extent of conversion to A-type. Conversely, scavenging endogenous Gβγ by co-expression of the C-terminal fragment of the β-adrenergic receptor kinase reduces the extent of conversion to A-type, The effect of Gβγ co-expression is occluded by treatment with dihydrocytochalasin B, a microfilament-disrupting agent shown previously by us to enhance the extent of conversion to A-type, and by overexpression of K(v)β1.1. Gβ₁γ₂ subunits interact directly with GST fusion fragments of K(v)1.1 and K(v)β1.1. Co-expression of Gβ₁γ₂ causes co-immunoprecipitation with K(v)1.1 of more K(v)β1.1 subunits. Thus, we suggest that Gβ₁γ₂ directly affects the interaction between K(v)1.1 and K(v)β1.1 during channel assembly which, in turn, disrupts the ability of the channel to interact with microfilaments, resulting in an increased extent of A-type conversion.