dtx k  (Danaher Inc)

Journal: The European Journal of Neuroscience

Article Title: Differential Modulation of Dopamine D2 Receptor on Somatostatin and Parvalbumin Interneurons in the CA1 Area of the Dorsal Hippocampus

doi: 10.1111/ejn.70176

Figure Lengend Snippet: Implication of Kv1.1 channel in D2R activation‐mediated changes in active membrane properties in SST‐INs and PV‐INs. (A) Left, I–V curve of leak‐subtracted current for tdTomato SST cells from −70 to −30 mV after application of quinpirole or quinpirole/DTX‐K. Mean of leak‐subtracted steady state at −40 mV in SST‐INs after application of quinpirole 10 μM with or without DTX‐ or at −30 mV. Left part: Ratio of decrease for SST‐INs at −30 mV after DTX‐K application. (B as in A) for tdTomato PV neurons after quinpirole 1 μM application with or without DTX‐K at −30 mV. Data are represented as mean ± SEM. Unpaired t ‐test and two‐way repeated measure ANOVA followed by Tukey test. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Article Snippet: Dendrotoxin‐K (DTX‐K) and SB‐216763 were purchased from Alomone lab and Hellobio, respectively.

Techniques: Activation Assay, Membrane, Patch Clamp

Journal: Cell & Bioscience

Article Title: Kv1.1 channel dysfunction in parvalbumin-positive interneurons contributes to anxiety-like behaviors in young adult presenilin 1/2 conditional double knockout mice

doi: 10.1186/s13578-025-01422-w

Figure Lengend Snippet: Reduced excitability of PV + interneurons and upregulated Kv1.1-mediated currents in vCA1 PV + interneurons of young adult PS cDKO; GAD mice. A Schematic illustration depicting the breeding process of PS cDKO; GAD mice (upper left), the experimental timeline (lower), and the recorded vCA1 PV + interneurons (upper right). B Representative confocal images showing the colabeling of GAD67 (green)-positive interneurons in the vCA1 region with PV (purple) and biocytin (red) antibodies. Scale bar, 50 μm. C Representative traces of action potentials (APs) obtained in response to a 50-pA step injection of current in PV + interneurons (left) and representative traces of single APs recorded in PV + interneurons (right) from WT; GAD and PS cDKO; GAD mice. Scale bar, left: 40 mV, 500 ms; right: 25 mV, 2.5 ms. D - E AP threshold ( D ) and firing frequency ( E ) of PV + interneurons from WT; GAD and PS cDKO; GAD mice in response to 50-pA current step injections ( n = 13 neurons from 5 mice for the WT; GAD group, n = 15 neurons from 5 mice for the PS cDKO; GAD group). F Schematic illustration depicting the experimental timeline and the recorded vCA1 “regular spiking” interneurons. G Representative confocal image showing the colabeling of GAD67 (green)-positive interneurons in the vCA1 region with biocytin (red) antibody but not with PV (purple) antibody. Scale bar, 50 μm. H - I AP threshold ( H ) and firing frequency ( I ) of “regular spiking” interneurons from WT; GAD and PS cDKO; GAD mice in response to 50-pA current step injections ( n = 11 neurons from 5 mice per group). J Schematic illustration depicting the experimental timeline, and the recorded vCA1 PNs. K Representative traces of APs obtained in response to a 50-pA step injection of current in PNs from WT; GAD and PS cDKO; GAD mice. Scale bar, 60 mV, 500 ms. L - M AP threshold ( L ) and firing frequency ( M ) of PNs from WT; GAD and PS cDKO; GAD mice in response to 50-pA current step injections ( n = 19 neurons from 4 mice per group). N Schematic illustration depicting the experimental timeline and the recorded vCA1 PV + interneurons. O Representative traces of K + currents elicited by trains of voltage steps from − 80 mV to + 20 mV in 10 mV increments from the holding potential of -80 mV in the absence or presence of DTx-K in PV + interneurons from WT; GAD and PS cDKO; GAD mice. Scale bar, 1 nA, 100 ms. P Current-voltage ( I - V ) relationship of total K + currents in PV + interneurons from WT; GAD and PS cDKO; GAD mice in the absence of DTx-K ( n = 7 neurons from 3 mice per group). Q I - V relationship of outward K + currents in PV + interneurons from WT; GAD and PS cDKO; GAD mice in the presence of DTx-K ( n = 7 neurons from 3 mice per group). R I - V curves showing DTx-K-sensitive K + currents obtained by subtracting the currents in the DTx-K condition from those in the TTX condition ( n = 7 neurons from 3 mice per group). S Representative immunoblot of Kv1.1 protein from ventral hippocampal lysates of WT; GAD and PS cDKO; GAD mice. Uncropped immunoblots are shown in Supplementary file. T Densitometry of the data presented in ( S ) ( n = 6 mice per group). U mRNA expression level of Kv1.1 from ventral hippocampal lysates of WT; GAD and PS cDKO; GAD mice ( n = 6 mice per group). Data are shown as mean ± S.E.M. Unpaired t test was applied in ( D ), ( H ), ( L ), and ( T - U ). Two-way Repeated Measures ANOVA with Bonferroni’s multiple comparisons test was applied in ( E ), ( I ), ( M ), and ( P - R ). * P < 0.05, ** P < 0.01, *** P < 0.001

Article Snippet: Additionally, the extracellular solution was coapplied with the K + channel inhibitor 4-AP (Sigma, St Louis, MO, USA) and the Kv1.1 inhibitor dendrotoxin-K (DTx-K) (Alomone labs, Jerusalem, Israel) to isolate the K + and Kv1.1-mediated currents, respectively.

Techniques: Confocal, Injection, Western Blot, Expressing, Immunofluorescence, Patch Clamp

Journal: Cell & Bioscience

Article Title: Kv1.1 channel dysfunction in parvalbumin-positive interneurons contributes to anxiety-like behaviors in young adult presenilin 1/2 conditional double knockout mice

doi: 10.1186/s13578-025-01422-w

Figure Lengend Snippet: Attenuated anxiety-like behaviors after genetic inhibition of Kv1.1 in the vCA1 of young adult PS cDKO mice. A Schematic illustration depicting the AAV-S5E2-PV-shRNA-Kv1.1-mCherry-WPRE (AAV-shKv1.1) and AAV-S5E2-PV-shRNA-scramble-mCherry-WPRE (AAV) viral vectors (upper) and the experimental timeline (lower). B Schematic illustration depicting bilateral stereotaxic injection of AAV-shKv1.1-mcherry into the vCA1 region (upper) and a representative image showing mCherry-labeled PV + interneurons in the whole hippocampus (HPC) of cDKO + AAV-shKv1.1 mice. Scale bar, 2000 μm. C The proportion of cells colabeled with PV antibody (green) and mCherry (red) among PV interneurons and mCherry-labeled neurons ( n = 6 slices from 3 mice). D Representative confocal images showing the colabeling of AAV-shKv1.1 (red)-positive interneurons in the vCA1 region with PV (green) antibody. Scale bar, 25 μm. E Representative confocal images showing the colabeling of PV-positive interneurons (green, stained with PV antibody) in the vCA1 region with Kv1.1 (purple) antibody. Scale bar, 25 μm. F The fluorescence intensity of Kv1.1 in PV-positive interneurons ( n = 6 slices from 3 mice). G - H Protein expression level of Kv1.1 from ventral hippocampal lysates (membrane fraction) of WT, cDKO, cDKO + AAV-shKv1.1, cDKO + AAV, and WT + AAV mice ( n = 6 mice per group). I mRNA expression level of Kv1.1 from ventral hippocampal lysates of WT, cDKO, cDKO + AAV-shKv1.1, cDKO + AAV, and WT + AAV mice ( n = 6 mice per group). Uncropped immunoblots are shown in Supplementary file. J - L Percentage of time spent in the margin zone ( J ), mean velocity ( K ), and total distance moved in the open field ( L ) in the open field test (OFT) ( n = 12 mice per group). M - P Time spent ( M ) and total distance traveled ( O ) in the light chamber, time spent in the dark chamber ( N ) and the number of transitions between light and dark chambers ( P ) in the light/dark box (LDB) test ( n = 12 mice per group). Q - S Open arm entries ( Q ), time spent in the open arm ( R ) and in the closed arm ( S ) in the elevated plus maze (EPM) test ( n = 12 mice per group). Data are shown as mean ± S.E.M. Unpaired t test was applied in ( C ). One-way ANOVA with Bonferroni’s multiple comparisons test was applied in ( F ) and ( H - S ). * P < 0.05, ** P < 0.01, *** P < 0.001

Article Snippet: Additionally, the extracellular solution was coapplied with the K + channel inhibitor 4-AP (Sigma, St Louis, MO, USA) and the Kv1.1 inhibitor dendrotoxin-K (DTx-K) (Alomone labs, Jerusalem, Israel) to isolate the K + and Kv1.1-mediated currents, respectively.

Techniques: Inhibition, shRNA, Injection, Labeling, Confocal, Staining, Fluorescence, Expressing, Membrane, Western Blot, Immunofluorescence, Patch Clamp

Journal: Cell & Bioscience

Article Title: Kv1.1 channel dysfunction in parvalbumin-positive interneurons contributes to anxiety-like behaviors in young adult presenilin 1/2 conditional double knockout mice

doi: 10.1186/s13578-025-01422-w

Figure Lengend Snippet: Ameliorated anxiety-like behaviors, decreased K + currents, and elevated excitability of PV + interneurons after pharmacological inhibition of Kv1.1 in the vCA1 of young adult PS cDKO mice. A Schematic illustration depicting bilateral stereotaxic injection of DTx-K into the vCA1 region (upper) and the experimental timeline (lower). Mice were injected once with DTx-K. B - D Percentage of time spent in the margin zone ( B ), mean velocity ( C ), and total distance moved in the open field ( D ) in the open field test (OFT) ( n = 10 mice per group). E - H Time spent ( E ) and total distance traveled ( G ) in the light chamber, time spent in the dark chamber ( F ) and the number of transitions between light and dark chambers ( H ) in the light/dark box (LDB) test ( n = 10 mice per group). I - K Open arm entries ( I ), time spent in the open arm ( J ) and in the closed arm ( K ) in the elevated plus maze (EPM) test ( n = 10 mice per group). L Schematic illustration depicting the recorded vCA1 PV + interneurons. M Representative traces of K + currents elicited by trains of voltage steps from − 80 mV to + 20 mV in 10 mV increments from the holding potential of -80 mV in PV + interneurons from WT + Veh (vehicle), cDKO + Veh, and cDKO + DTx-K mice. Scale bar, 1 nA, 100 ms. N Current-voltage ( I - V ) relationship of K + currents in PV + interneurons from WT + Veh, cDKO + Veh, and cDKO + DTx-K mice ( n = 15 neurons from 6 mice for the WT + Veh group, n = 29 neurons from 9 mice for the cDKO + Veh group, n = 20 neurons from 8 mice for the cDKO + DTx-K group). O Representative traces of action potentials (APs) obtained in response to a 50-pA step injection of current in PV + interneurons from WT + Veh, cDKO + Veh, and cDKO + DTx-K mice. Scale bar, 40 mV, 500 ms. P - Q AP threshold ( P ) and firing frequency ( Q ) of PV + interneurons from WT + Veh, cDKO + Veh, and cDKO + DTx-K mice in response to 50-pA current step injections ( n = 14 neurons from 4 mice for the WT + Veh group, n = 16 neurons from 4 mice for the cDKO + Veh group, n = 13 neurons from 4 mice for the cDKO + DTx-K group). Data are shown as mean ± S.E.M. One-way ANOVA with Bonferroni’s multiple comparisons test was applied in ( B - K ) and ( P ). Two-way Repeated Measures ANOVA with Bonferroni’s multiple comparisons test was applied in ( N ) and ( Q ). * P < 0.05, ** P < 0.01, *** P < 0.001. NS, not significant

Article Snippet: Additionally, the extracellular solution was coapplied with the K + channel inhibitor 4-AP (Sigma, St Louis, MO, USA) and the Kv1.1 inhibitor dendrotoxin-K (DTx-K) (Alomone labs, Jerusalem, Israel) to isolate the K + and Kv1.1-mediated currents, respectively.

Techniques: Inhibition, Injection, Patch Clamp

Journal: Cell & Bioscience

Article Title: Kv1.1 channel dysfunction in parvalbumin-positive interneurons contributes to anxiety-like behaviors in young adult presenilin 1/2 conditional double knockout mice

doi: 10.1186/s13578-025-01422-w

Figure Lengend Snippet: Elevated excitability of PV + interneurons after genetic inhibition of Kv1.1 in the vCA1 of young adult PS cDKO mice. A Schematic illustration depicting the recorded vCA1 PV + interneurons. B Current-voltage ( I - V ) relationship of K + currents in PV + interneurons from WT, cDKO, cDKO + AAV-shKv1.1, cDKO + AAV, and WT + AAV mice ( n = 8 neurons from 4 mice per group). C - D AP threshold ( C ) and firing frequency ( D ) of PV + interneurons from WT, cDKO, cDKO + AAV-shKv1.1, cDKO + AAV, and WT + AAV mice in response to 50-pA current step injections ( n = 14 neurons from 4 mice for the WT group, n = 15 neurons from 4 mice for the cDKO group, n = 16 neurons from 4 mice for the cDKO + AAV-shKv1.1 group, n = 12 neurons from 4 mice for the cDKO + AAV group, n = 15 neurons from 4 mice for the WT + AAV group). E Schematic illustration depicting the recorded vCA1 PNs. F Representative traces of spontaneous excitatory postsynaptic currents (sEPSCs) and spontaneous inhibitory postsynaptic currents (sIPSCs) recorded in PNs from WT, cDKO, cDKO + AAV-shKv1.1, cDKO + AAV, and WT + AAV mice. Scale bar, 20 pA, 200 ms. G - H sEPSCs frequency ( G ) and amplitude ( H ) ( n = 17 neurons from 5 mice per group). I - J sIPSCs frequency ( I ) and amplitude ( J ) ( n = 17 neurons from 5 mice per group). K - L Charge transfer of sEPSCs ( K ) and sIPSCs ( L ) ( n = 17 neurons from 5 mice per group). M The ratio of sEPSC/sIPSC charge transfer ( n = 17 neurons from 5 mice per group). Data are shown as mean ± S.E.M. Two-way Repeated Measures ANOVA with Bonferroni’s multiple comparisons test was applied in ( B ) and ( D ). One-way ANOVA with Bonferroni’s multiple comparisons test was applied in ( C ) and ( G - M ). * P < 0.05, ** P < 0.01, *** P < 0.001

Article Snippet: Additionally, the extracellular solution was coapplied with the K + channel inhibitor 4-AP (Sigma, St Louis, MO, USA) and the Kv1.1 inhibitor dendrotoxin-K (DTx-K) (Alomone labs, Jerusalem, Israel) to isolate the K + and Kv1.1-mediated currents, respectively.

Techniques: Inhibition, Patch Clamp

Journal: Cell & Bioscience

Article Title: Kv1.1 channel dysfunction in parvalbumin-positive interneurons contributes to anxiety-like behaviors in young adult presenilin 1/2 conditional double knockout mice

doi: 10.1186/s13578-025-01422-w

Figure Lengend Snippet: A schematic diagram for Kv1.1 in vCA1 PV + interneurons regulating anxiety-like behaviors in young adult PS cDKO mice

Article Snippet: Additionally, the extracellular solution was coapplied with the K + channel inhibitor 4-AP (Sigma, St Louis, MO, USA) and the Kv1.1 inhibitor dendrotoxin-K (DTx-K) (Alomone labs, Jerusalem, Israel) to isolate the K + and Kv1.1-mediated currents, respectively.

Techniques: