Format

Send to

Choose Destination
Biochim Biophys Acta Mol Cell Res. 2017 Oct;1864(10):1537-1544. doi: 10.1016/j.bbamcr.2017.06.016. Epub 2017 Jun 23.

Functional interaction of the two-pore domain potassium channel TASK-1 and caveolin-3.

Author information

1
Division of Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
2
Division of Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA. Electronic address: hu.175@osu.edu.

Abstract

The two-pore domain potassium channel TASK-1 is strongly expressed in the heart and has been shown to modulate the resting membrane potential and action potential. However, little is known about the regulation of TASK-1 channels. The present study was designed to determine whether TASK-1 is modulated by caveolin-3, a primary structural protein of cardiac caveolae. Functional studies with the whole-cell voltage clamp technique showed that the expression of caveolin-3 decreased recombinant TASK-1 currents significantly in HEK293T cells, and this effect was prevented by co-expressing the dominant negative mutant caveolin-3 P104L. Immunofluorescence imaging revealed the colocalization of TASK-1 and caveolin-3. Co-immunoprecipitation analysis indicated that caveolin-3 associated with TASK-1. When co-expressed with caveolin-3 P104L, the fluorescence intensity of caveolin-3 on the cell periphery was reduced. This agrees with the functional evidence that caveolin-3 P104L prevented the inhibitory effect of caveolin-3 on TASK-1 currents, possibly via reducing the plasma membrane targeting of caveolin-3. Further, our data from cardiomyocytes suggest that TASK-1 is associated with caveolin-3. In summary, our study indicates that TASK-1 is functionally regulated by caveolin-3, possibly via association with each other on the cell surface. These results point out a novel mechanism in the regulation of TASK-1.

KEYWORDS:

Caveolin-3; Caveolin-3 P104L; TASK-1

PMID:
28648645
DOI:
10.1016/j.bbamcr.2017.06.016
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center