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Mol Brain. 2014 Nov 19;7:80. doi: 10.1186/s13041-014-0080-z.

TWIK-1 contributes to the intrinsic excitability of dentate granule cells in mouse hippocampus.

Author information

  • 1Korea Institute of Science and Technology (KIST), Center for Functional Connectomics, Seoul, 136-791, Republic of Korea. yarishkin@gmail.com.
  • 2Korea Institute of Science and Technology (KIST), Center for Functional Connectomics, Seoul, 136-791, Republic of Korea. daylee@hanmail.net.
  • 3Korea Research Institute of Bioscience and Biotechnology (KRIBB), Stem Cell Research Center, Daejeon, 305-806, Republic of Korea. daylee@hanmail.net.
  • 4Korea Institute of Science and Technology (KIST), Center for Functional Connectomics, Seoul, 136-791, Republic of Korea. trek1747@gmail.com.
  • 5School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul, 136-703, Republic of Korea. chois007@gmail.com.
  • 6Korea Institute of Science and Technology (KIST), Center for Functional Connectomics, Seoul, 136-791, Republic of Korea. dionysusjh@naver.com.
  • 7Neuroscience Program, University of Science and Technology (UST), Daejeon, 305-350, Republic of Korea. dionysusjh@naver.com.
  • 8Korea Institute of Science and Technology (KIST), Center for Functional Connectomics, Seoul, 136-791, Republic of Korea. cjl@kist.re.kr.
  • 9Neuroscience Program, University of Science and Technology (UST), Daejeon, 305-350, Republic of Korea. cjl@kist.re.kr.
  • 10Korea Institute of Science and Technology (KIST), Center for Functional Connectomics, Seoul, 136-791, Republic of Korea. emhwang@kist.re.kr.
  • 11Neuroscience Program, University of Science and Technology (UST), Daejeon, 305-350, Republic of Korea. emhwang@kist.re.kr.
  • 12Korea Institute of Science and Technology (KIST), Center for Functional Connectomics, Seoul, 136-791, Republic of Korea. jaeyong68@korea.ac.kr.
  • 13School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul, 136-703, Republic of Korea. jaeyong68@korea.ac.kr.

Abstract

BACKGROUND:

Two-pore domain K(+) (K2P) channels have been shown to modulate neuronal excitability. However, physiological function of TWIK-1, the first identified member of the mammalian K2P channel family, in neuronal cells is largely unknown.

RESULTS:

We found that TWIK-1 proteins were expressed and localized mainly in the soma and proximal dendrites of dentate gyrus granule cells (DGGCs) rather than in distal dendrites or mossy fibers. Gene silencing demonstrates that the outwardly rectifying K(+) current density was reduced in TWIK-1-deficient granule cells. TWIK-1 deficiency caused a depolarizing shift in the resting membrane potential (RMP) of DGGCs and enhanced their firing rate in response to depolarizing current injections. Through perforant path stimulation, TWIK-1-deficient granule cells showed altered signal input-output properties with larger EPSP amplitude values and increased spiking compared to control DGGCs. In addition, supra-maximal perforant path stimulation evoked a graded burst discharge in 44% of TWIK-1-deficient cells, which implies impairment of EPSP-spike coupling.

CONCLUSIONS:

These results showed that TWIK-1 is functionally expressed in DGGCs and contributes to the intrinsic excitability of these cells. The TWIK-1 channel is involved in establishing the RMP of DGGCs; it attenuates sub-threshold depolarization of the cells during neuronal activity, and contributes to EPSP-spike coupling in perforant path-to-granule cell synaptic transmission.

PMID:
25406588
PMCID:
PMC4240835
DOI:
10.1186/s13041-014-0080-z
[PubMed - indexed for MEDLINE]
Free PMC Article
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