Figure 3.

Arcuate NPY neurons from Tg2576 brain slices or exogenous Aβ_1–42-treated WT brain slices have a left shift in the peak L-type Ca²⁺ current I–V curve that can be reversed by the L-type Ca²⁺ channel blocker nimodipine (NMD). A, L-type Ca²⁺ currents in arcuate NPY neurons from Tg2576 brain slices show a propensity for channel opening close to the resting potential compared with arcuate NPY neurons from WT brain slices. Representative traces are shown using the holding potential −60 mV to different stepped potentials from −50 to 20 mV (showing −30 to 10 mV). B, I–V relationships for L-type Ca²⁺ currents in arcuate NPY neurons from WT or Tg2576 brain slices. There was a left shift in the peak L-type Ca²⁺ current I–V curve in arcuate NPY neurons from Tg2576 brain slices compared with WT brain slices. The peak L-type Ca²⁺ current in the I–V curve occurred at −20 mV for arcuate NPY neurons from Tg2576 brain slices compared with 0 mV for arcuate NPY neurons from WT slices. At −20 mV, arcuate NPY neurons from Tg2576 brain slices have significantly higher L-type Ca²⁺ currents compared with arcuate NPY neurons from WT brain slices. Data are represented as L-type Ca²⁺ current density (pA/pF). n = 19–27 per group from ≥ 12 mice per group. Statistical analysis: two-tailed unpaired Student's t test (t = 2.832, df = 45, p = 0.0069). C, The peak L-type Ca²⁺ current I–V curve in arcuate NPY neurons from WT brain slices treated with oligomeric Aβ_1–42 (100 nm) recapitulates the left shift seen in arcuate NPY neurons from Tg2576 brain slices. The peak L-type Ca²⁺ current in the I–V curve occurred between −10 mV and −20 mV for arcuate NPY neurons after application of oligomeric Aβ_1–42 (100 nm) slices compared with 0 mV at baseline (vehicle treatment). At −20 mV, arcuate NPY neurons from oligomeric Aβ_1–42 (100 nm)-treated WT brain slices have significantly higher L-type Ca²⁺ currents compared with arcuate NPY neurons from vehicle-treated WT brain slices. Data are represented as L-type Ca²⁺ current density (pA/pF). n = 6 per group from ≥ 4 mice per group. Statistical analysis: two-tailed paired Student's t test (t = 4.598, df = 5, p = 0.0059). D, L-type Ca²⁺ current induced at −10 mV were significantly decreased after application of nimodipine (2 μm) in arcuate NPY neurons from WT brain slices, Tg2576 brain slices, and WT brain slices treated with oligomeric Aβ_1–42 (100 nm). n = 5–8 per group from ≥ 4 mice per group. Statistical analysis: two-tailed paired Student's t test (WT: t = 9.806, df = 7, p < 0.0001; Tg2576: t = 4.694, df = 5, p = 0.0054; Aβ_1–42: t = 2.912, df = 4, p = 0.0436). Data are mean ± SEM. *p < 0.05. **p < 0.01. ***p < 0.001.