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 Gβ 1 γ 2 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. Gβ 1 γ 2 subunits interact directly with GST fusion fragments of K v 1.1 and K v β1.1. Co‐expression of Gβ 1 γ 2 causes co‐immunoprecipitation with K v 1.1 of more K v β1.1 subunits. Thus, we suggest that Gβ 1 γ 2 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.