Identification and characterization of alternative splice variants of the mouse Trek2/Kcnk10 gene

K. Mirkovic, K. Wickman

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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 languageEnglish (US)
Pages (from-to)11-18
Number of pages8
JournalNeuroscience
Volume194
DOIs
StatePublished - Oct 27 2011

Bibliographical note

Funding 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:
Copyright 2013 Elsevier B.V., All rights reserved.

Keywords

  • 2-pore domain
  • Central nervous system
  • Excitability
  • Gene expression
  • Potassium channel

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