Abstract

Modulation of A-type voltage-gated K⁺ channels can produce plastic changes in neuronal signaling. It was shown that the delayed-rectifier K_v1.1 channel can be converted to A-type upon association with K_v1.1 subunits; the conversion is only partial and is modulated by phosphorylation and microfilaments. Here we show that, in Xenopus oocytes, expression of G₁₂ subunits concomitantly with the channel (composed of K_v1.1 and K_v1.1 subunits), but not after the channel's expression in the plasma membrane, increases the extent of conversion to A-type. Conversely, scavenging endogenous G by co-expression of the C-terminal fragment of the -adrenergic receptor kinase reduces the extent of conversion to A-type. The effect of G 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_v1.1. G₁₂ subunits interact directly with GST fusion fragments of K_v1.1 and K_v1.1. Co-expression of G₁₂ causes co-immunoprecipitation with K_v1.1 of more K_v1.1 subunits. Thus, we suggest that G₁₂ directly affects the interaction between K_v1.1 and K_v1.1 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.