title: Sparks and puffs in oligodendrocyte progenitors: cross talk between ryanodine receptors and inositol trisphosphate receptors.
abstract: Investigating how calcium release from the endoplasmic reticulum (ER) is triggered and coordinated is crucial to our understanding of how oligodendrocyte progenitor cells (OPs) develop into myelinating cells. Sparks and puffs represent highly localized Ca(2+) release from the ER through ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP(3)Rs), respectively. To study whether sparks or puffs trigger Ca(2+) waves in OPs, we performed rapid high-resolution line scan recordings in fluo-4-loaded OP processes. We found spontaneous and evoked sparks and puffs, and we have identified functional cross talk between IP(3)Rs and RyRs. Local events evoked using the IP(3)-linked agonist methacholine (MeCh) showed significantly different morphology compared with events evoked using the caffeine analog 3,7-dimethyl-1-propargylxanthine (DMPX). Pretreatment with MeCh potentiated DMPX-evoked events, whereas inhibition of RyRs potentiated events evoked by low concentrations of MeCh. Furthermore, activation of IP(3)Rs but not RyRs was critical for Ca(2+) wave initiation. Using immunocytochemistry, we show OPs express the specific Ca(2+) release channel subtypes RyR3 and IP(3)R2 in patches along OP processes. RyRs are coexpressed with IP(3)Rs in some patches, but IP(3)Rs are also found alone. This differential distribution pattern may underlie the differences in local and global Ca(2+) signals mediated by these two receptors. Thus, in OPs, interactions between IP(3)Rs and RyRs determine the spatial and temporal characteristics of calcium signaling, from microdomains to intracellular waves.
authors.affiliation: National Institute of Child Health and Human Development, National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
authors.forename: L L
authors.initials: LL
authors.lastname: Haak
authors.forename: L S
authors.initials: LS
authors.lastname: Song
authors.forename: T F
authors.initials: TF
authors.lastname: Molinski
authors.forename: I N
authors.initials: IN
authors.lastname: Pessah
authors.forename: H
authors.initials: H
authors.lastname: Cheng
authors.forename: J T
authors.initials: JT
authors.lastname: Russell
mesh_terms: D000814:Aniline Compounds; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047028:Macrocyclic Compounds; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009836:Oligodendroglia / Q000166:cytology; D010080:Oxazoles / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D011940:Receptor Aggregation / Q000502:physiology; D020239:Receptor Cross-Talk / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014966:Xanthenes
chemical_list: D000814:Aniline Compounds; D015220:Calcium Channels; D004791:Enzyme Inhibitors; C409648:Fluo 4; D005456:Fluorescent Dyes; D053496:Inositol 1,4,5-Trisphosphate Receptors; D047028:Macrocyclic Compounds; D018721:Muscarinic Agonists; D010080:Oxazoles; D058915:Purinergic P1 Receptor Antagonists; D018160:Receptors, Cytoplasmic and Nuclear; D011976:Receptors, Muscarinic; D019837:Ryanodine Receptor Calcium Release Channel; D014966:Xanthenes; C108644:xestospongin A; D016210:Methacholine Chloride; C057837:3,7-dimethyl-1-propargylxanthine; D010738:Type C Phospholipases; D013805:Theobromine; D002118:Calcium