NIH R01 · 2024
Collective Ryanodine Receptor Operation at Release Sites
Ryanodine receptors (RyRs) mediate Ca-induced Ca release (CICR) from the sarcoplasmic reticulum (SR). The SR has discrete Ca release sites, each with a cluster of RyRs. During diastole, single -RyRs open infrequently, but when one does, the Ca it releases may ignite localized inter-RyR CICR (a spark). Abnormally frequent or large sparks can evoke propagating Ca waves, ventricular tachycardia and sudden cardiac death. RyRs operate inter-dependently at release sites. Opening of any RyR in a cluster invariably and dynamically (spatially & temporally) alters local [Ca]’s (cytosolic & intra-SR). These [Ca] changes may activate neighboring RyRs. The clustered RyR-geometry at release sites and the…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.