Pflügers Archiv - European Journal of Physiology

, Volume 465, Issue 12, pp 1715–1726 | Cite as

G protein modulation of K2P potassium channel TASK-2

A role of basic residues in the C terminus domain
  • Carolina Añazco
  • Gaspar Peña-Münzenmayer
  • Carla Araya
  • L. Pablo Cid
  • Francisco V. SepúlvedaEmail author
  • María Isabel NiemeyerEmail author
Ion channels, receptors and transporters


TASK-2 (K2P5.1) is a background K+ channel opened by extra- or intracellular alkalinisation that plays a role in renal bicarbonate handling, central chemoreception and cell volume regulation. Here, we present results that suggest that TASK-2 is also modulated by Gβγ subunits of heterotrimeric G protein. TASK-2 was strongly inhibited when GTP-γ-S was used as a replacement for intracellular GTP. No inhibition was present using GDP-β-S instead. Purified Gβγ introduced intracellularly also inhibited TASK-2 independently of whether GTP or GDP-β-S was present. The effects of GTP-γ-S and Gβγ subunits were abolished by neutralisation of TASK-2 C terminus double lysine residues K257–K258 or K296–K297. Use of membrane yeast two hybrid (MYTH) experiments and immunoprecipitation assays using tagged proteins gave evidence for a physical interaction between Gβ1 and Gβ2 subunits and TASK-2, in agreement with expression of these subunits in proximal tubule cells. Co-immunoprecipitation was impeded by mutating C terminus K257–K258 (but not K296–K297) to alanines. Gating by extra- or intracellular pH was unaltered in GTP-γ-S-insensitive TASK-2-K257A-K258A mutant. Shrinking TASK-2-expressing cells in hypertonic solution decreased the current to 36 % of its initial value. The same manoeuvre had a significantly diminished effect on TASK-2-K257A-K258A- or TASK-2-K296-K297-expressing cells, or in cells containing intracellular GDP-β-S. Our data are compatible with the concept that TASK-2 channels are modulated by Gβγ subunits of heterotrimeric G protein. We propose that this modulation is a novel way in which TASK-2 can be tuned to its physiological functions.


TASK-2 G protein Background conductance Patch-clamp Cell volume regulation 



We are grateful to Drs. Jürgen Daut (Marburg), Stéphane A. Laporte (Montréal) and Carlos B. González (Valdivia) for cDNAs for TASK-3, and AT1 and V1a receptors. Mauricio Bórquez is acknowledged for his help with some of the experiments. Financial support was obtained from Fondecyt grants 1090478 and 3085021. The Centro de Estudios Científicos (CECS) is funded by the Chilean Government through the Centres of Excellence Base Financing Program of Conicyt.

Supplementary material

424_2013_1314_MOESM1_ESM.docx (26 kb)
ESM 1 (DOCX 25 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Carolina Añazco
    • 1
    • 2
  • Gaspar Peña-Münzenmayer
    • 1
    • 3
  • Carla Araya
    • 1
  • L. Pablo Cid
    • 1
  • Francisco V. Sepúlveda
    • 1
    Email author
  • María Isabel Niemeyer
    • 1
    Email author
  1. 1.Centro de Estudios Científicos (CECs)ValdiviaChile
  2. 2.Nephrology & Hypertension, Department of MedicineVanderbilt University Medical CenterNashvilleUSA
  3. 3.National Institute of Dental and Craniofacial Research, National Institutes of HealthBethesdaUSA

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