TRESK background potassium channel is not gated at the helix bundle crossing near the cytoplasmic end of the pore

Miklós Lengyel, G. Czirják, Péter Enyedi

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article numbere0197622
JournalPLoS One
Volume13
Issue number5
DOIs
Publication statusPublished - May 1 2018

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Tandem Pore Domain Potassium Channels
Phosphorylation
potassium channels
spinal cord
Spinal Cord
phosphorylation
dephosphorylation
Membranes
Point Mutation
Membrane Potentials
point mutation
Chemical activation
membrane potential
Kinetics
kinetics
mutants

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

TRESK background potassium channel is not gated at the helix bundle crossing near the cytoplasmic end of the pore. / Lengyel, Miklós; Czirják, G.; Enyedi, Péter.

In: PLoS One, Vol. 13, No. 5, e0197622, 01.05.2018.

Research output: Contribution to journalArticle

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