Am J Physiol Cell Physiol. 2016 Dec 1;311(6):C884-C894.

Functional and molecular identification of a TASK-1 potassium channel regulating chloride secretion through CFTR channels in the shark rectal gland: implications for cystic fibrosis.

Telles CJ1,2, Decker SE1,2, Motley WW1,2, Peters AW1,2, Mehr AP1,2, Frizzell RA3,2, Forrest JN Jr4,2.
1 Nephrology Division, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.
2 Mount Desert Island Biological Laboratory, Salisbury Cove, Maine.
3 Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and.
4 Nephrology Division, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut;


In the shark rectal gland (SRG), apical chloride secretion through CFTR channels is electrically coupled to a basolateral K+ conductance whose type and molecular identity are unknown. We performed studies in the perfused SRG with 17 K+channel inhibitors to begin this search. Maximal chloride secretion was markedly inhibited by low-perfusate pH, bupivicaine, anandamide, zinc, quinidine, and quinine, consistent with the properties of an acid-sensitive, four-transmembrane, two-pore-domain K+channel (4TM-K2P). Using PCR with degenerate primers to this family, we identified a TASK-1 fragment in shark rectal gland, brain, gill, and kidney. Using 5′ and 3′ rapid amplification of cDNA ends PCR and genomic walking, we cloned the full-length shark gene (1,282 bp), whose open reading frame encodes a protein of 375 amino acids that was 80% identical to the human TASK-1 protein. We expressed shark and human TASK-1 cRNA in Xenopus oocytes and characterized these channels using two-electrode voltage clamping. Both channels had identical current-voltage relationships (outward rectifying) and a reversal potential of -90 mV. Both were inhibited by quinine, bupivicaine, and acidic pH. The pKa for current inhibition was 7.75 for shark TASK-1 vs. 7.37 for human TASK-1, values similar to the arterial pH for each species. We identified this protein in SRG by Western blot and confocal immunofluorescent microscopy and detected the protein in SRG and human airway cells. Shark TASK-1 is the major K+channel coupled to chloride secretion in the SRG, is the oldest 4TM 2P family member identified, and is the first TASK-1 channel identified to play a role in setting the driving force for chloride secretion in epithelia. The detection of this potassium channel in mammalian lung tissue has implications for human biology and disease.


cystic fibrosis transmembrane conductance regulator; four transmembrane two pore; shark rectal gland; task-1 K+ channel

PMID: 27653983; DOI: 10.1152/ajpcell.00030.2016