Characterization and regulation of wild-type and mutant TASK-1 two pore domain potassium channels indicated in pulmonary arterial hypertension.

ABSTRACT:

Key points

The TASK-1 channel gene (KCNK3) has been identified as a possible disease-causing gene in heritable pulmonary arterial hypertension (PAH). In the present study, we show that novel mutated TASK-1 channels, seen in PAH patients, have a substantially reduced current compared to wild-type TASK-1 channels. These mutated TASK-1 channels are located at the plasma membrane to the same degree as wild-type TASK-1 channels. ONO-RS-082 and alkaline pH 8.4 both activate TASK-1 channels but do not recover current through mutant TASK-1 channels. We show that the guanylate cyclase activator, riociguat, a novel treatment for PAH, enhances current through TASK-1 channels but does not recover current through mutant TASK-1 channels.

Abstract

Pulmonary arterial hypertension (PAH) affe

SUBMITTER: Cunningham KP 

PROVIDER: S-EPMC6376074 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature