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

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-beta-cyclodextrin (M beta CD), 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 M beta CD was not altered in mutant channels with different apparent affinities for PIP2.

Automated summary

The activity of neuronal Kv7.2/Kv7.3 channels is regulated by both PIP2 and cholesterol. Cholesterol depletion enhances the interaction between Kv7.2/Kv7.3 channels and PIP2, while acute membrane cholesterol depletion does not affect the sensitivity of mutant channels with different affinities for PIP2.