Sparks and puffs in oligodendrocyte progenitors: Cross talk between ryanodine receptors and inositol trisphosphate receptors

Investigating how calcium release from the endoplasmic reticulum (ER) is tr iggered and coordinated is crucial to our understanding of how oligodendroc yte progenitor cells (OPs) develop into myelinating cells. Sparks and puffs represent highly localized Ca2+ release from the ER through ryanodine rece ptors (RyRs) and inositol trisphosphate receptors (IP(3)Rs), respectively. To study whether sparks or puffs trigger Ca2+ waves in OPs, we performed ra pid high-resolution line scan recordings in fluo-4-loaded OP processes. We found spontaneous and evoked sparks and puffs, and we have identified funct ional cross talk between IP(3)Rs and RyRs. Local events evoked using the IP 3-linked agonist methacholine (MeCh) showed significantly different morphol ogy compared with events evoked using the caffeine analog 3,7-dimethyl-1-pr opargylxanthine (DMPX). Pretreatment with MeCh potentiated DMPX-evoked even ts, whereas inhibition of RyRs potentiated events evoked by low concentrati ons of MeCh. Furthermore, activation of IP(3)Rs but not RyRs was critical f or Ca2+ wave initiation. Using immunocytochemistry, we show OPs express the specific Ca2+ release channel subtypes RyR3 and IP(3)R2 in patches along O P 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 Ca2+ signals mediated by these two rece ptors. Thus, in OPs, interactions between IP(3)Rs and RyRs determine the sp atial and temporal characteristics of calcium signaling, from microdomains to intracellular waves.