Related Experiment Video
Updated: Aug 9, 2026

Mutagenesis and Functional Analysis of Ion Channels Heterologously Expressed in Mammalian Cells
Published on: October 2, 2010
Localization of TREK-2 K+ channel domains that regulate channel kinetics and sensitivity to pressure, fatty acids and
1Department of Physiology and Biophysics, Finch University of Health Sciences, The Chicago Medical School, IL 60064, USA. donghee.kim@finchcms.edu
Abstract:
TREK-2, a member of the tandem-pore K+ channel family, is activated by membrane stretch, unsaturated free fatty acids and acidic conditions, and exhibits unique open channel kinetics. To identify the regions responsible for these properties, we studied the role of the cytoplasmic regions of TREK-2. Deletion of the N-terminus had no effect on any aspect of TREK-2 function. Deletion of the C-terminus or its substitution with that of TASK-3 abolished the sensitivity to free fatty acids and intracellular pH (pHi), and reduced the sensitivity to pressure. The regions that allow activation by free fatty acids and low pHi were localized to 25- and 10-amino-acid domains, respectively, close to the fourth transmembrane segment. Substitution of KKTKEE, a charged region near the proximal C-terminus, with uncharged amino acids produced little change in TREK-2 function; however, its deletion abolished sensitivity to fatty acids and low pH, indicating that this region is structurally very important. The TREK-2 C-terminus was also found to be critical for its channel opening in bursts as well as for its increased basal activity. Thus, the C-terminus endows TREK-2 with unique channel kinetics and the ability to be gated by free fatty acids and low pHi, and with increased mechanosensitivity.
Related Concept Videos
Non-gated Ion Channels
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Ligand-gated Ion Channels
Three Subfamilies of Ligand-gated Ion Channels
Ligand-gated ion channels fall into three subfamilies. The 'Cys-loop' includes the nicotinic acetylcholine receptors, γ-aminobutyric acid (GABA), glycine, and 5-hydroxytryptamine receptors. The second one is the 'Pore-loop' channels that include the...
Mechanically-gated Ion Channels
Amplifying Signals via Second Messengers
Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Mechanically-gated Ion Channels

