Potassium channel TASK-5 forms functional heterodimers with TASK-1 and TASK-3 to break its silence
Susanne Rinné, Florian Schick, Kirsty Vowinkel, Sven Schütte, Cornelius Krasel, Silke Kauferstein, Martin Schäfer, Aytuğ K. Kiper, Thomas Müller, Niels Decher
Abstract
channel for which there is no functional data available, since it was reported in 2001 as non-functional and thus "silent". Here we show that TASK-5 channels are indeed non-functional as homodimers, but are involved in the formation of functional channel complexes with TASK-1 and TASK-3. TASK-5 negatively modulates the surface expression of TASK channels, while the heteromeric TASK-5-containing channel complexes located at the plasma membrane are characterized by changes in single-channel conductance, Gq-coupled receptor-mediated channel inhibition, and sensitivity to TASK modulators. The unique pharmacology of TASK-1/TASK-5 heterodimers, affected by a common polymorphism in KCNK15, needs to be carefully considered in the future development of drugs targeting TASK channels. Our observations provide an access to study TASK-5 at the functional level, particularly in malignant cancers associated with KCNK15.