Crosstalk between cholesterol and PIP2 in the regulation of Kv7.2/Kv7.3 channels

Abstract

The activity of neuronal Kv7.2/Kv7.3 channels is critically dependent on PIP₂ and finely modulated by cholesterol. Here, we report the crosstalk between cholesterol and PIP₂ in the regulation of Kv7.2/Kv7.3 channels. Our results show that currents passing through Kv7.2/Kv7.3 channels in cholesterol-depleted cells, by acute application of methyl-β-cyclodextrin (MβCD), were less sensitive to PIP₂ dephosphorylation strategies than those of control cells, suggesting that cholesterol depletion enhances the Kv7.2/Kv7.3-PIP₂ interaction. In contrast, the sensitivity of Kv7.2/Kv7.3 channels to acute membrane cholesterol depletion by MβCD was not altered in mutant channels with different apparent affinities for PIP₂.

Keywords: PIP2; cholesterol; cyclodextrin; ion channels; lipids.