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Chunk #15 — Results — Distinctive Maturation‐Specific Changes in Functional Ion Channel Expression in hPSC‐Derived Oligodendrocyte‐Lineage Cells

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Maturation and electrophysiological properties of human pluripotent stem cell-derived oligodendrocytes.
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Rodent OPCs and oligodendrocytes exhibit cell‐type specific voltage‐gated ion channel expression profiles, which are correlated to developmentally defined oligodendroglial immunohistochemical markers and underpin the properties of the membrane currents described above 24, 25. Depolarizing current injections applied to PDGFRα+‐OPCs gave rise to tetrodotoxin (TTX, 300 nM) sensitive spikes (16 from 18 cells) and indicate the functional expression of voltage‐gated Na+ (Na V) channels (Fig. 3A). As has been reported for rodent OPCs 26 spiking behavior did not fit the criteria that would be used to classify neuronal action potential firing as these spike amplitudes did not generally cross 0 mV. The existence of native spiking and non‐spiking OPC populations has been subject of numerous recent studies 26, 27, 28, and we therefore further isolated and characterized the Na V‐channels expressed in hPSC‐oligodendroglial cells using a depolarizing voltage‐step protocol (Fig. 3B, 3C). We found 89% of ESC‐ and 100% of iPSC‐derived PDGFRα+‐OPCs possessed TTX‐sensitive currents. However, all functional TTX‐sensitive Na V‐channel expression (current density) is lost in week 3 O4+‐oligodendrocytes derived from the ES line (Fig. 3D) and iPS lines (data not shown).