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 Ca2+ release from the ER through ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP3Rs), respectively. To study whether sparks or puffs trigger Ca2+ 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 IP3Rs and RyRs. Local events evoked using the IP3-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 Iow concentrations of MeCh. Furthermore, activation of IP3Rs but not RyRs was critical for Ca2+ wave initiation. Using immunocytochemistry, we show OPs express the specific Ca2+ release channel subtypes RyR3 and IP3R2 in patches along OP processes. RyRs are coexpressed with IP3Rs in some patches, but IP3Rs are also found alone. This differential distribution pattern may underlie the differences in local and global Ca2+ signals mediated by these two receptors. Thus, in OPs, interactions between IP3Rs and RyRs determine the spatial and temporal characteristics of calcium signaling, from microdomains to intracellular waves.