In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 25, No. 38 ( 2005-09-21), p. 8601-8610
Abstract:
Oligodendrocyte maturation has been defined based on expression of developmentally regulated antigens. However, transitions at early stages of the lineage have not been functionally characterized fully in situ . Combining 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNP)-promoter driven enhanced green fluorescent protein expression and whole-cell capacitance measurements permitted a reliable distinction between subcortical white matter NG2 + oligodendrocyte progenitors (OPs) and O4 + preoligodendrocytes (pre-OLs) in situ . We focused on K + channels because their expression has been associated previously with the proliferation and differentiation potential of OPs. Using whole-cell patch clamp, we observed a downregulation of the delayed outward-rectifying current ( I KDR ) between the NG2 + and O4 + stages but no significant changes in transient K + -channel current ( I KA ) amplitude. Tyrosine kinase inhibition in NG2 + cells reduced I KDR amplitude with no effect on I KA , which mimicked the endogenous changes observed between OPs and pre-OLs. Tyrosine kinase inhibition also reduced the proliferative capacity of NG2 + OPs in slice cultures. Conversely, acute platelet-derived growth factor receptor-α (PDGFR-α) activation caused an increase of I KDR in NG2 + but not in O4 + cells. Consistent with this finding, PDGFR-α immunoreactivity was confined to NG2 + cells with undetectable levels in O4 + cells, suggesting that PDGFR-α signaling is absent in pre-OLs in situ . Importantly, the PDGF-induced increase of I KDR in NG2 + cells was prevented by tyrosine kinase inhibition. Together, these data indicate that PDGFR-α and tyrosine kinase activity act via a common pathway that influences functional expression of K + channels and proliferative capacity of OPs in situ .
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.2122-05.2005
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
2005
detail.hit.zdb_id:
1475274-8
SSG:
12
