Potassium channel TASK-5 forms functional heterodimers with TASK-1 and TASK-3 to break its silence.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39215006.
- Also identified by DOI 10.1038/s41467-024-51288-8 and PMC identifier 11364637.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
TASK-5 (KCNK15) belongs to the acid-sensitive subfamily of two-pore domain potassium (K<sub>2P</sub>) channels, which includes TASK-1 and TASK-3. TASK-5 stands out as K<sub>2P</sub> 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.
Medical subject headings
- Nerve Tissue Proteins
- Potassium Channels, Tandem Pore Domain