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TRESK background potassium channel is not gated at the helix bundle crossing near the cytoplasmic end of the pore.
- Source :
-
PloS one [PLoS One] 2018 May 15; Vol. 13 (5), pp. e0197622. Date of Electronic Publication: 2018 May 15 (Print Publication: 2018). - Publication Year :
- 2018
-
Abstract
- Two-pore domain K+ channels (K2P) are responsible for background K+ currents and regulate the resting membrane potential and cellular excitability. Their activity is controlled by a large variety of physicochemical factors and intracellular signaling pathways. The majority of these effects converge on the intracellular C-terminus of the channels, resulting in the modification of the gating at the selectivity filter. Another gating mechanism, the activation gate at the helix bundle crossing is also well documented in other K+ channel families, however, it remains uncertain whether this type of gating is functional in K2P channels. The regulation of TWIK-related spinal cord K+ channel (TRESK) is different from the other K2P channels. Regulatory factors acting via the C-terminus are not known, instead channel activity is modified by the phosphorylation/dephosphorylation of the unusually long intracellular loop between the 2nd and 3rd transmembrane segments. These unique structural elements of the regulation lead us to examine channel gating at the bundle crossing region. Ba2+ was applied to the intracellular side of excised membrane patches and the characteristics of the channel block were determined. We compared the kinetics of the development of Ba2+ block when the channels were phosphorylated (inhibited) or dephosphorylated (activated) and also in different mutants mimicking the two functional states. Neither the phosphorylation/dephosphorylation nor the point mutations influenced the development of Ba2+ block, suggesting that the conformational changes of the bundle crossing region do not contribute to the phosphorylation-dependent gating of TRESK.
- Subjects :
- Amino Acid Substitution
Animals
Barium metabolism
Cell Cycle Proteins chemistry
Cell Cycle Proteins genetics
Cell Cycle Proteins metabolism
Cyclic AMP-Dependent Protein Kinases metabolism
Cytoplasm metabolism
Female
HEK293 Cells
Humans
Ion Channel Gating
Kinetics
Kv1.3 Potassium Channel antagonists & inhibitors
Kv1.3 Potassium Channel metabolism
Mice
Oocytes metabolism
Patch-Clamp Techniques
Phosphorylation
Point Mutation
Potassium Channels chemistry
Potassium Channels genetics
Potassium Channels, Tandem Pore Domain antagonists & inhibitors
Potassium Channels, Tandem Pore Domain chemistry
Potassium Channels, Tandem Pore Domain genetics
Protein Conformation
Protein Serine-Threonine Kinases chemistry
Protein Serine-Threonine Kinases genetics
Protein Serine-Threonine Kinases metabolism
Recombinant Proteins chemistry
Recombinant Proteins genetics
Recombinant Proteins metabolism
Xenopus laevis
Potassium Channels metabolism
Potassium Channels, Tandem Pore Domain metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 13
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 29763475
- Full Text :
- https://doi.org/10.1371/journal.pone.0197622