Fig. 3

Functional validation of KCNN4 mRNA copy number changes in detected human pyramidal cells. Waveforms of action potentials evoked by depolarizing current injections (a) and of extracellularly evoked EPSPs (b) responded differently to the serial application of the small- and intermediate-conductance calcium activated potassium channel activator NS309 (500 nM) and TRAM34 (1 μM), an inhibitor of intermediate-conductance calcium activated potassium channels. The descending phase of action potentials and EPSPs was shortened in pyramidal cells recorded in brain slices prepared from the Edema group, but remained unchanged in pyramidal neurons of the Control group and in fast spiking interneurons of the Edema group. Traces shown are population averages. Confocal images of immunoreactions with antibodies against Kcnn4 performed simultaneously on samples of the Control and Edema groups showing a cross section of the gray matter (c) and part of layer 3 similar to areas where electrophysiological experiments were performed (d). Pyramidal cells were not labeled in the Control group and moderate Kcnn4 positivity was detected in pyramidal cells (p) of the Edema group. In addition, intense immunolabeling for Kcnn4 was detected in glial cells resembling astrocytes and interlaminar glia in both groups of patients