Two-pore domain K+ (K2P) channels underlie leak or background potassium conductances in many cells. The Trek subfamily of K2P channels, which includes Trek1/Kcnk2 and Trek2/Kcnk10 and has been implicated in depression, nociception, and cognition, exhibits complex regulation and can modulate cell excitability in response to a wide array of stimuli. While alternative translation initiation and alternative splicing contribute to the structural and functional diversity of Trek1, the impact of post-transcriptional modifications on the expression and function of Trek2 is unclear. Here, we characterized two novel splice isoforms of the mouse Trek2 gene. One variant is a truncated form of Trek2 that possesses two transmembrane segments and one pore domain (Trek2-1p), while the other (Trek2b) differs from two known mouse Trek2 isoforms (Trek2a and Trek2c) at the extreme amino terminus. Both Trek2-1p and Trek2b, and Trek2a and Trek2c, showed prominent expression in the mouse CNS. Expression patterns of the Trek2 variants within the CNS were largely overlapping, though some isoform-specific differences were noted. Heterologous expression of Trek2-1p yielded no novel whole-cell currents in transfected human embryonic kidney (HEK) 293 cells. In contrast, expression of Trek2b correlated with robust K+ currents that were ~fivefold larger than currents measured in cells expressing Trek2a or Trek2c, a difference mirrored by significantly higher levels of Trek2b found at the plasma membrane. This study provides new insights into the molecular diversity of Trek channels and suggests a potential role for the Trek2 amino terminus in channel trafficking and/or stability.
|Original language||English (US)|
|Number of pages||8|
|State||Published - Oct 27 2011|
Bibliographical noteFunding Information:
The authors would like to thank members of the Wickman laboratory for providing helpful comments on this manuscript. This work was supported by NIH grants RO1 MH061933 , P50 DA011806 , R21 DA029343 (K.W.), and T32 DA07234 (K.M.).
Copyright 2013 Elsevier B.V., All rights reserved.
- 2-pore domain
- Central nervous system
- Gene expression
- Potassium channel