Fig. 2: Synaptically-evoked K+ uptake through Kir4.1 channels is reduced in Fmr1 knockout astrocytes. | Nature Communications

Fig. 2: Synaptically-evoked K+ uptake through Kir4.1 channels is reduced in Fmr1 knockout astrocytes.

From: Astroglial Kir4.1 potassium channel deficit drives neuronal hyperexcitability and behavioral defects in Fragile X syndrome mouse model

Fig. 2

a Hippocampus scheme illustrating simultaneous recording of neuronal activity as field excitatory postsynaptic potentials (fEPSPs, light blue) and astrocyte current (dark blue) with extracellular or patch-clamp electrodes, respectively, in response to Schaffer collateral (SC) stimulation. b Simultaneous recordings of fEPSP (light blue, trace 1) and synaptically-evoked astrocyte current (dark blue, trace 1) in response to SC stimulation (0.05 Hz) in the presence of picrotoxin (control). Addition of glutamate receptor antagonists CPP and NBQX inhibits fEPSP (light blue, trace 2) and potassium component of astrocyte current (dark blue, trace 2). Subtraction of CPP + NBQX-insensitive component (2) from the total astrocyte current (1) reveals synaptically-evoked astroglial K+ current (IK). This current is carried by Kir4.1 channels as confirmed by the absence of IK in Kir4.1−/− mice (purple). Scale bars, upper: 0.2 mV, 10 ms; lower left: 10 pA, 10 ms; lower right: 20 pA, 0.2 s. c Representative traces of pharmacologically isolated astrocyte IK in WT (dark blue) and Fmr1 KO mice (magenta). Arrows indicate stimulation artifact. Scale bar: 10 pA, 1 s. Quantification of astrocyte IK properties reveals: (d) decrease in IK peak amplitude (P < 0.001, t = −5.429, df = 28), (e) decrease in IK peak normalized to fEPSP slope (P = 0.005, U = 45), (f) decrease in charge (P < 0.001, U = 24), (g) increase in time of peak (P = 0.018, t = −2.510, df = 28), (h) increase in rise time (P = 0.014, t = −2.614, df = 28) and i decrease in decay time (P = 0.005. U = 44) in Fmr1 KO (n = 15 astrocytes from 15 slices in 11 mice) as compared to WT (n = 15 astrocytes from 15 slices in 14 mice). Data are presented as mean values ± SEM (d–i). *P < 0.05, **P < 0.01, ***P < 0.001. Statistical significance was calculated using two-sided unpaired Student’s t test (d, g, h) or two-sided Mann–Whitney test (e, f, i). Source data are provided as a Source Data file.

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