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

Oleg Yarishkin, Da Y ong Lee, Eunju Kim, Chang Hoon Cho, Jae H youk Choi, Changjoon Lee, Eun M i Hwang, Jae-Yong Park

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10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)80
Number of pages1
JournalMolecular Brain
Volume7
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Medicine(all)

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    Yarishkin, O., Lee, D. Y. O., Kim, E., Cho, C. H., Choi, J. H. Y., Lee, C., Hwang, E. M. I., & Park, J-Y. (2014). TWIK-1 contributes to the intrinsic excitability of dentate granule cells in mouse hippocampus. Molecular Brain, 7, 80. https://doi.org/10.1186/s13041-014-0080-z