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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.
A related channel TASK-3 also implicated in inhalational anesthetic actions is insensitive to xenon.
Thus, we performed WES and identified an additional mutation in the KCNK17 gene encoding the K2P potassium channel TASK-4.
In this line, using WES and functional studies, we now link the first cardiac disorder (PCCD) to the K2P channel TASK-4.
Due to the severe phenotype, we performed whole-exome sequencing (WES) and identified an additional mutation in the KCNK17 gene encoding the K2P potassium channel TASK-4.
The potassium channel TASK-1 is inhibited at 21% oxygen in Nox4-expressing cells (but not in Nox4-RNAi cells), and this inhibition is relieved by hypoxia.
In addition, just recently, multiple mutations in the acid-sensitive K2P channel TASK-1 (KCNK3) were reported to cause familial and idiopathic pulmonary arterial hypertension (Ma et al, 2013).
In the present study, WES was utilized to identify the KCNK17 gene encoding the K2P channel TASK-4 as a novel disease gene that might be functionally relevant for cardiac conduction disorders.
In a single report, familial Birk Barel syndrome that is characterized by mental retardation, hypotonia, and facial and skeletal dysmorphism is caused by a mutation in the paternally imprinted potassium channel TASK-3 (KCNK9) on chromosome 8q24.3 (Barel et al, 2008).
The expression of TASK-4 in Purkinje fibers was as high as for the K2P channel TASK-1 (KCNK3), which is known to be preferentially expressed in the conduction system of mouse and chick hearts (Fig 3B) (Graham et al, 2006).
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