title: TWIK-1 contributes to the intrinsic excitability of dentate granule cells in mouse hippocampus.
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.
authors.affiliation: Korea Institute of Science and Technology (KIST), Center for Functional Connectomics, Seoul, 136-791, Republic of Korea. yarishkin@gmail.com.
authors.forename: Oleg
authors.initials: O
authors.lastname: Yarishkin
authors.affiliation: Korea Institute of Science and Technology (KIST), Center for Functional Connectomics, Seoul, 136-791, Republic of Korea. daylee@hanmail.net.|Korea Research Institute of Bioscience and Biotechnology (KRIBB), Stem Cell Research Center, Daejeon, 305-806, Republic of Korea. daylee@hanmail.net.
authors.forename: Da Yong
authors.initials: DY
authors.lastname: Lee
authors.affiliation: Korea Institute of Science and Technology (KIST), Center for Functional Connectomics, Seoul, 136-791, Republic of Korea. trek1747@gmail.com.
authors.forename: Eunju
authors.initials: E
authors.lastname: Kim
authors.affiliation: School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul, 136-703, Republic of Korea. chois007@gmail.com.
authors.forename: Chang-Hoon
authors.initials: CH
authors.lastname: Cho
authors.affiliation: Korea Institute of Science and Technology (KIST), Center for Functional Connectomics, Seoul, 136-791, Republic of Korea. dionysusjh@naver.com.|Neuroscience Program, University of Science and Technology (UST), Daejeon, 305-350, Republic of Korea. dionysusjh@naver.com.
authors.forename: Jae Hyouk
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Korea Institute of Science and Technology (KIST), Center for Functional Connectomics, Seoul, 136-791, Republic of Korea. cjl@kist.re.kr.|Neuroscience Program, University of Science and Technology (UST), Daejeon, 305-350, Republic of Korea. cjl@kist.re.kr.
authors.forename: C Justin
authors.initials: CJ
authors.lastname: Lee
authors.affiliation: Korea Institute of Science and Technology (KIST), Center for Functional Connectomics, Seoul, 136-791, Republic of Korea. emhwang@kist.re.kr.|Neuroscience Program, University of Science and Technology (UST), Daejeon, 305-350, Republic of Korea. emhwang@kist.re.kr.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Hwang
authors.affiliation: Korea Institute of Science and Technology (KIST), Center for Functional Connectomics, Seoul, 136-791, Republic of Korea. jaeyong68@korea.ac.kr.|School of Biosystem and Biomedical Science, College of Health Science, Korea University, Seoul, 136-703, Republic of Korea. jaeyong68@korea.ac.kr.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D000200:Action Potentials; D000818:Animals; D018891:Dentate Gyrus / Q000166:cytology* / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials; D055785:Gene Knockdown Techniques; D008297:Male; D008810:Mice, Inbred C57BL; D015221:Potassium Channels / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000172:deficiency / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
chemical_list: C486372:Kcnk1 protein, mouse; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain