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Chunk #21 — Results — Expression of Arginine‐Edited GluA2 AMPAR Subunits Is Upregulated in hPSC‐Derived Oligodendrocytes

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Maturation and electrophysiological properties of human pluripotent stem cell-derived oligodendrocytes.
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GluA2 subunits are predominantly RNA edited in approximately 99% of central nervous system mRNA transcripts, where editing results in an arginine codon replacing a glutamine codon in the M2 re‐entrant loop region of the ion channel. The presence of the edited GluA2 [GluA2(R)] subunit in AMPAR complexes imparts low single‐channel conductance, low Ca2+ permeability, and insensitivity to polyamine‐mediated channel block 35. We examined the composition of AMPARs expressed by hPSC‐derived OPCs and oligodendrocytes by estimating the mean unitary single‐channel conductance using nonstationary fluctuation analysis (Fig. 6E, 6F 21). Unitary conductances were estimated by plotting current‐variance plots from AC‐ and DC‐coupled recordings of currents elicited by AMPA (10 μM) in the presence of cyclothiazide (10 μM) or in some recordings, AMPA (100 μM) alone (Fig. 6G). For the ES line, the mean AMPAR conductance of PDGFRα+‐OPCs decreased from 8.0 ± 0.2 pS (n = 14, N = 4) to 2.9 ± 0.1 pS in week 3 O4+‐oligodendrocytes (n = 4, N = 2, p<0.001, unpaired t tests, Fig. 6H). Equivalent data were also obtained from iPSC‐derived oligodendrocyte‐lineage cells (Fig. 6H). The