Article

Regulation of L-Type Ca++ Currents and Process Morphology in White Matter Oligodendrocyte Precursor Cells by Golli-Myelin Proteins

Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California, 90095, USA.
Glia (Impact Factor: 6.03). 08/2010; 58(11):1292-303. DOI: 10.1002/glia.21008
Source: PubMed

ABSTRACT

The golli myelin basic proteins are expressed in oligodendroglial precursor cells (OPCs) where they play a role in regulating Ca(2+) homeostasis. During depolarization, they influence process outgrowth and migration through their action on voltage-operated Ca(2+) channels (VOCCs). To identify ion channels that are modulated by golli, we examined the electrophysiological properties of VOCCs in OPCs in the white matter of golli knock-out and control mice. OPCs exhibited two distinct Ca(2+) channels, which were distinguished by their voltage dependence and pharmacological profiles and which exhibited many of the hallmarks of LVA/T-type and HVA/L-type Ca(2+) channels. The density of high-voltage-activated (HVA) currents was reduced in OPCs recorded in golli-KO tissue, while low-voltage-activated (LVA) currents remained unaltered in these cells. These data indicate that golli exerts an exclusive influence on L-type Ca(2+) channels in OPCs. Oligodendrocytes (OLs) also displayed LVA and HVA currents, although the density of these currents was much reduced at this developmental stage. These currents were not altered in golli-KO OLs showing the influence of golli on L-type Ca(2+) channels is restricted to a specific time-window during the course of oligodendroglial development. The actions of golli on OPC L-type Ca(2+) channels were accompanied by changes in process morphology, including a reduction in process complexity and the appearance of enlarged varicosities that decorated these cellular processes. These data on L-type Ca(2+) channels and process development provide in situ evidence for the influence of golli on VOCCs, and offer an explanation for the hypomyelination observed in the brains of golli-KO mice.

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Available from: Daniel Fulton, Jul 18, 2014
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    • "The function of these process extensions, and whether they are also apparent on more mature ensheathments awaits further investigation since similar observations are yet to be reported from other time-lapse studies. Varicosities are frequently observed along the processes of immature OL (Fulton et al., 2010). These swellings have been shown to contain enlarged mitochondria (Berger et al., 1991) and may therefore represent foci of enhanced metabolic activity, as S.M. Rassul et al. / Neuropharmacology xxx (2015) 1e11 2 Please cite this article in press as: Rassul, S.M., et al., Live-imaging in the CNS: New insights on oligodendrocytes, myelination, and their responses to inflammation, Neuropharmacology (2015), http://dx.doi.org/10.1016/j.neuropharm.2015.09.011 "
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    • "irm the effect of UDP - glucose in inhibiting Ca 2þ influx through L - type VOCCs observed in Ca 2þ imaging experi - ments . Data in the literature demonstrate that OPs , either in culture ( Blankenfeld et al . , 1992 ; Kettenmann et al . , 1991 ; Verkhratsky et al . , 1990 ; Williamson et al . , 1997 ) or in brain slices ( Berger et al . , 1992 ; Fulton et al . , 2010 ) , present both T - type and L - type Ca 2þ channels whose expression decreases dur - ing cell maturation ( Berger et al . , 1992 ; Blankenfeld et al . , 1992 ; Verkhratsky et al . , 1990 ) . In order to isolate I Ca in cul - tured OPs , K þ conductances were blocked by dialyzing the cell with a Cs þ - based pipette solution and by ext"
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    Full-text · Article · Jul 2013 · Glia
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    • "The Golli protein isoforms come first developmentally, being expressed in OLGs at intermediate stages of differentiation (Givogri et al. 2001; Tosic et al. 2002; Campagnoni and Campagnoni 2004; Fulton et al. 2010a). There are both karyophilic and plasma membrane-targeted forms, and these proteins promote OLG migration and process extension, and enhance potassium-induced calcium influx via multiple kinase signaling pathways (Paez et al. 2007, 2009a, b, 2010, 2012; Fulton et al. 2010b). The 21.5-kDa MBP isoform is the first of the classic isoforms to be synthesized, starting with OPCs. "
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