Figure 8. Schematic representation of intracellular Ca²⁺ signaling in primary cultured rat ONHAs – differential distribution of intracellular Ca²⁺ channels provides the molecular substrate for distinct and temporally and spatially independent subcellular Ca²⁺ signaling patterns.

IP₃R2 is the major subtype of IP₃Rs in ONHAs, expressed differentially in the membranes of the nuclear envelope, which are contiguous with the membranes of the ER. Ca²⁺ release from IP₃R2 in the nuclear envelope into the nucleoplasm is amplified through RyR2 by Ca²⁺-induced Ca²⁺ release (CICR; black dotted arrows), leading to Ca²⁺-mediated regulation of gene expression. All types of RyR contribute to Ca²⁺ release into the ER via amplification of IP₃R1-mediated Ca²⁺ release potentially mediating non-genomic functions of Ca²⁺signaling in ONHAs.