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Chunk #18 — 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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In contrast to decreases in I K‐ and I A‐channel expression, differentiation of rodent oligodendrocytes from OPCs is associated with an increase in inwardly rectifying K+ (K ir) channel expression 24. Specifically the K ir4.1 subunit has been reported to play a pivotal role in oligodendrocyte development, myelination and setting the resting membrane potential (RMP) of native mature oligodendrocytes 29 but see 30. There are no selective blockers that can be used to isolate pharmacologically K ir4.1‐mediated currents and therefore we confirmed immunohistochemically the presence of K ir4.1 subunits in O4+/MBP+‐oligodendrocytes and PDGFRα+‐OPCs (Fig. 5A). Subsequent analysis of K ir channel expression in the ES‐line (Fig. 5B, 5C) indicated an increase in inwardly rectifying current densities in week 3 oligodendrocytes compared with both week 1 oligodendrocytes and PDGFRα+‐OPCs (Fig. 5D). This was also accompanied by an increase in the detection of K ir currents (56% in PDGFRα+‐OPCs and 100% in week 3 O4+‐oligodendrocytes). Associated with this, we observed a hyperpolarization of the RMP from –39.2 ± 0.4 mV in OPCs to –53.5 ± 1.0 mV in week 3 oligodendrocytes (Fig. 5E). Thus, the maturation of human oligodendrocytes displays a comparable profile of potassium channel conductances to that seen in rodents.