Yarishkin, Oleg Lee, Da Yong Kim, Eunju Cho, Chang-Hoon Choi, Jae Hyouk Lee, C. Justin Hwang, Eun Mi Park, Jae-Yong 2024-01-20T08:31:23Z 2024-01-20T08:31:23Z 2021-09-02 2014-11-19 1756-6606 https://pubs.kist.re.kr/handle/201004/126110 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. English BMC POTASSIUM CHANNELS NEURONAL EXCITABILITY SUMOYLATION SILENCES K+ CURRENTS GYRUS MEMBRANE KCNK CONDUCTANCE EXPRESSION PLASTICITY TWIK-1 contributes to the intrinsic excitability of dentate granule cells in mouse hippocampus Article 10.1186/s13041-014-0080-z 1 MOLECULAR BRAIN, v.7 MOLECULAR BRAIN 7 scie scopus 000345930300001 2-s2.0-84947040368 Neurosciences Neurosciences & Neurology Article POTASSIUM CHANNELS NEURONAL EXCITABILITY SUMOYLATION SILENCES K+ CURRENTS GYRUS MEMBRANE KCNK CONDUCTANCE EXPRESSION PLASTICITY K2P channel TWIK-1 Intrinsic excitability Dentate gyrus granule cell