Unknown

Dataset Information

0

Cholesterol-Binding Sites in GIRK Channels: The Devil is in the Details.


ABSTRACT: In recent years, it has become evident that cholesterol plays a direct role in the modulation of a variety of ion channels. In most cases, cholesterol downregulates channel activity. In contrast, our earlier studies have demonstrated that atrial G protein inwardly rectifying potassium (GIRK) channels are upregulated by cholesterol. Recently, we have shown that hippocampal GIRK currents are also upregulated by cholesterol. A combined computational-experimental approach pointed to putative cholesterol-binding sites in the transmembrane domain of the GIRK2 channel, the primary subunit in hippocampal GIRK channels. In particular, the principal cholesterol-binding site was located in the center of the transmembrane domain in between the inner and outer ?-helices of 2 adjacent subunits. Further studies pointed to a similar cholesterol-binding site in GIRK4, a major subunit in atrial GIRK channels. However, a close look at a sequence alignment of the transmembrane helices of the 2 channels reveals surprising differences among the residues that interact with the cholesterol molecule in these 2 channels. Here, we compare the residues that form putative cholesterol-binding sites in GIRK2 and GIRK4 and discuss the similarities and differences among them.

SUBMITTER: Rosenhouse-Dantsker A 

PROVIDER: S-EPMC5815411 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

altmetric image

Publications

Cholesterol-Binding Sites in GIRK Channels: The Devil is in the Details.

Rosenhouse-Dantsker Avia A  

Lipid insights 20180214


In recent years, it has become evident that cholesterol plays a direct role in the modulation of a variety of ion channels. In most cases, cholesterol downregulates channel activity. In contrast, our earlier studies have demonstrated that atrial G protein inwardly rectifying potassium (GIRK) channels are upregulated by cholesterol. Recently, we have shown that hippocampal GIRK currents are also upregulated by cholesterol. A combined computational-experimental approach pointed to putative cholest  ...[more]

Similar Datasets

| S-EPMC7019021 | biostudies-literature
| S-EPMC5865623 | biostudies-literature
| S-EPMC3477822 | biostudies-other
| S-EPMC7335934 | biostudies-literature
| S-EPMC7990506 | biostudies-literature
| S-EPMC5496853 | biostudies-other
| S-EPMC5113978 | biostudies-literature
| S-EPMC3786416 | biostudies-literature
| S-EPMC7274256 | biostudies-literature
| S-EPMC10435609 | biostudies-literature