Ryanodine receptors (RyR) are intracellular Ca2+ channels localized in the endoplasmic reticulum, where they act as critical mediators of Ca2+-induced Ca2+ calcium release (CICR). In the brain, mammals express in both neurons, and non-neuronal cells, a combination of the three RyR-isoforms (RyR1-3). Pharmacological approaches, which do not distinguish between isoforms, have indicated that RyR-isoforms contribute to brain function. However, isoform-specific manipulations have revealed that RyR-isoforms display different subcellular localizations and are differentially associated with neuronal function. These findings raise the need to understand RyR-isoform specific transcriptional regulation, as this knowledge will help to elucidate the causes of neuronal dysfunction for a growing list of brain disorders that show altered RyR channel expression and function.
Keywords: Excitation-transcription coupling, Calcium signaling, Neuronal function and dysfunction; Ryanodine receptor isoforms.
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