| Annotated protein: | Potassium channel subfamily K member 1 (Inward rectifying potassium channel protein TWIK-1). Gene symbol: KCNK1. Taxonomy: Mus musculus (Mouse). Uniprot ID: O08581 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ KCNK1 |
| Ontology domain: | Biological Process |
| SynGO term: | voltage-gated ion channel activity involved in regulation of postsynaptic membrane potential (GO:1905030) |
| Synapse type(s): | hippocampus |
| Annotated paper: | Yarishkin O, et al. "TWIK-1 contributes to the intrinsic excitability of dentate granule cells in mouse hippocampus" Mol Brain. 2014 Nov 19;7:80 PMID:25406588 |
| Figure(s): | Figure 2, 3 and 4 |
| Annotation description: | DGGCs are known to functionally express several types of K+ channels, including the inwardly rectifying (Kir) and voltage-gated (Kv) potassium channels. Therefore, to measure TWIK-1-mediated currents in dentate gyrus granule cells, a mixture of the commonly-used Kir channel blocker, Cs+ (1 mM) and Kv channel blocker, TEA (2 mM) was used. Figure 2: TWIK-1 contributes to the electrical properties of the DGGC plasma membrane, behaving as an outwardly rectifying K+ channel in DGGCs. administration of Cs+/TEA caused a marked reduction of both outward and inward currents (by 25.7 ± 3.04% and 75.87 ± 3.48% at 40 mV and -150 mV, respectively). Notably, Cs+/TEA almost completely abolished the inwardly rectifying component of the I-V curve, while the outwardly-rectifying component was also seen to be reduced. The remaining Cs+/TEA-resistant currents in naïve DGGCs had a prominent outwardly rectifying I-V relationship with a current density of -2.4 ± 0.3 pA/pF at -150 mV and 58.6 ± 2.4 pA/pF at 40 mV. TWIK-1 shRNA significantly reduced only outward currents (-2.5 ± 0.2 pA/pF at -150 mV and 38.1 ± 1.7 pA/pF at 40 mV), while the Scrambled shRNA (Sc shRNA) control did not affect the I-V relationship (-3.1 ± 0.4 pA/pF at -150 mV and 53.5 ± 2.3 pA/pF at 40 mV: Figures 2B, C). The reversal potential of the currents in TWIK-1-deficient granule cells was shifted towards a positive voltage range (-67.8 ± 1.4 mV) compared to that in naïve or Scrambled control cells (-76.5 ± 1.1 mV and -74.7 ± 1.6 mV, respectively: Figure 2D), implying a lack of potassium conductance in TWIK-1-deficient cells. Figure 3: TWIK-1 contributes to the intrinsic excitability of DGGCs by the establishment of the resting membrane potential (RMP) and by providing a potassium conductance, which attenuates membrane depolarization in response to excitatory current injection. The firing rates in TWIK-1 shRNA-infected cells were higher than those in naïve or Sc shRNA-infected cells (Figures3A, B). the RMP of TWIK-1-deficient DGGCs was significantly depolarized (-70.6 ± 0.6 mV), compared to both naïve (-74.6 ± 0.9 mV) and Scrambled control cells (-77.3 ± 1.2 mV: Additional file 2: Table S1). Figure 4: TWIK-1 deficiency in dentate granule cells causes the enhanced amplitude of evoked EPSPs in response to perforant path stimulation. Comparative analysis of eEPSP amplitudes showed a significant difference between TWIK-1-deficient granule cells and naïve or Scrambled control cells over a stimulus intensity range of 150 - 250μA, with larger values for EPSP amplitude being observed in TWIK-1-deficient cells (Figure4A). unaltered paired-pulse ratios calculated from a series of paired-pulse interval stimulations of TWIK-1-deficient DGGCs, rule out any alteration in release probability at perforant path terminals after TWIK-1 knockdown in DG (Figure4B). |
| Evidence tracking, Biological System: | Intact tissue |
| Evidence tracking, Protein Targeting: | RNAi / shRNA |
| Evidence tracking, Experiment Assay: | Whole-cell patch clamp |
| Annotator(s): | Dnyanada Sahasrabudhe (ORCID:0000-0003-2916-7616) Guus Smit (ORCID:0000-0002-2286-1587) Matthijs Verhage (ORCID:0000-0002-2514-0216) |
| Lab: | Department of Functional Genomics, Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands |
| SynGO annotation ID: | 4559 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |