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 2ϩ release from the ER through ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP 3 Rs), respectively. To study whether sparks or puffs trigger Ca 2ϩ 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 2ϩ wave initiation. Using immunocytochemistry, we show OPs express the specific Ca 2ϩ 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 2ϩ 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.

Molecular Cloning of Mouse Type 2 and Type 3 Inositol 1,4,5-Trisphosphate Receptors and Identification of a Novel Type 2 Receptor Splice Variant

“…The average width at half-maximal amplitude of puffs evoked by photolysis of caged IP 3 in Xenopus oocytes has already been reported to be 1.9 m (65). The size of puffs observed in various cultured cells (60) and oligodendrocytes (61) is similar to that observed in Xenopus oocytes despite the large difference in size of the cells. High resolution line scan imaging showed that Ca 2ϩ puffs in Xenopus oocytes arise as a result of Ca 2ϩ release from a fixed point source that is smaller than the limit of optical resolution (ϳ0.25 m) (66).…”

Action Potential-Evoked and Ryanodine-Sensitive Spontaneous Ca2+Transients at the Presynaptic Terminal of a Developing CNS Inhibitory Synapse

“…Similar bursts of ryanodine-sensitive calcium transients have been observed in heart muscle (Cheng et al, 1993) in the presence of low concentrations of ryanodine and in oligodendrocyte progenitor cells (Haak et al, 2001) after application of 3,7-Dimethyl-1-propargylaxanthine (a caffeine analog). The triggering mechanism for SCaTs in our system is not yet known, although direct and indirect evidence allow us to rule out some possible mecha-nisms.…”

Requirement of ryanodine receptors for pacemaker Ca2+ activity in ICC and HEK293 cells

“…Ca 2+ sparks have been identified in cardiac, skeletal and smooth muscle cells (Bootman et al, 1995), where RyR2, RyR1 and RyR2/3 are predominantly expressed, respectively (Ogawa et al, 2002). In oligodendrocyte progenitors, Ca 2+ sparks and puffs have been recorded and cross-talk between RyR3 and IP3R2 is speculated (Haak et al, 2001). It has been suggested that IP3R2 is essential to induced Ca 2+ puffs and waves, while RyR3 generates the Ca 2+ sparks.…”