Formation of functional heterodimers by TREK-1 and TREK-2 two-pore domain potassium channel subunits

Miklós Lengyel, G. Czirják, P. Enyedi

Research output: Contribution to journalArticle

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Abstract

Two-pore domain (K2P) potassium channels are the major molecular correlates of the background (leak) K+ current in a wide variety of cell types. They generally play a key role in setting the resting membrane potential and regulate the response of excitable cells to various stimuli. K2P channels usually function as homodimers, and only a few examples of heteromerization have been previously reported. Expression of the TREK (TWIK-related K+ channel) subfamily members of K2P channels often overlaps in neurons and in other excitable cells. Here, we demonstrate that heterologous coexpression of TREK-1 and TREK-2 subunits results in the formation of functional heterodimers. Taking advantage of a tandem construct (in which the two different subunits were linked together to enforce heterodimerization), we characterized the biophysical and pharmacological properties of the TREK-1/TREK-2 current. The heteromer was inhibited by extracellular acidification and by spadin similarly to TREK-1, and its ruthenium red sensitivity was intermediate between TREK-1 and TREK-2 homodimers. The heterodimer has also been distinguished from the homodimers by its unique single channel conductance. Assembly of the two different subunits was confirmed by coimmunoprecipitation of epitope-tagged TREK-1 and TREK-2 subunits, coexpressed in Xenopus oocytes. Formation of TREK-1/TREK-2 channels was also demonstrated in native dorsal root ganglion neurons indicating that heterodimerization may provide greater diversity of leak K+ conductances also in native tissues.

Original languageEnglish
Pages (from-to)13649-13661
Number of pages13
JournalJournal of Biological Chemistry
Volume291
Issue number26
DOIs
Publication statusPublished - Jun 24 2016

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Potassium Channels
Neurons
Ruthenium Red
Acidification
Epitopes
Spinal Ganglia
Tissue
Xenopus
Membranes
Membrane Potentials
Oocytes
Pharmacology

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Formation of functional heterodimers by TREK-1 and TREK-2 two-pore domain potassium channel subunits. / Lengyel, Miklós; Czirják, G.; Enyedi, P.

In: Journal of Biological Chemistry, Vol. 291, No. 26, 24.06.2016, p. 13649-13661.

Research output: Contribution to journalArticle

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