Distant cytosolic residues mediate a two-way molecular switch that controls the modulation of inwardly rectifying potassium (Kir) channels by cholesterol and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)).

ABSTRACT:

Background

Cholesterol modulates inwardly rectifying potassium (Kir) channels.

Results

A two-way molecular cytosolic switch controls channel modulation by cholesterol and PI(4,5)P(2).

Conclusion

Cholesterol and PI(4,5)P(2) induce a common gating pathway of Kir2.1 despite their opposite impact on channel function.

Significance

These findings provide insights into structure-function relationship of ion channels and contribute to understanding of the mechanisms underlying their regulation by lipids. Inwardly rectifying potassium (Kir) channels play an important role in setting the resting membrane potential and modulating membrane excitability. An emerging feature of several Kir channels is that they are regulated by cholesterol. However, the mechanism by which ch

SUBMITTER: Rosenhouse-Dantsker A 

PROVIDER: S-EPMC3504743 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature