Related Experiment Video
Updated: Feb 18, 2026

Functional Characterization of Endogenously Expressed Human RYR1 Variants
Published on: June 9, 2021
Pb2+ modulates ryanodine receptors from the endoplasmic reticulum in rat brain
Qiyue Jia1, Guihua Du1, Yu Li2
1Department of Occupational Health and Toxicology, School of Public Health, Nanchang University, BaYi Road 461, Nanchang, Jiangxi Province 330006, PR China; Jiangxi Provincial Key Laboratory of Preventive Medicine, Nanchang University, BaYi Road 461, Nanchang, Jiangxi Province 330006, PR China.
Abstract:
Although the neurotoxic mechanism of lead (Pb2+) has been extensively studied, it is not well understood. The effects of Pb2+ on free cytosolic calcium (Ca2+) concentration and calcium-regulated events have been suggested to be major mechanisms in Pb2+ toxicity. Based on our previous findings that Pb2+ changes calcium release through ryanodine receptors (RyRs), the modulation of endoplasmic reticulum (ER) vesicular RyRs by Pb2+ was investigated further in the present study. The results of [3H]ryanodine binding assays showed that in the presence of a free Ca2+ concentration ([Ca2+]f) of 100μM, Pb2+ modulated the equilibrium of [3H]ryanodine binding to brain RyRs, with a U-type dose-response curve, where minimal binding was observed at a free Pb2+ concentration ([Pb2+]f) of 0.39μM. This modulation was also observed over a time course. Scatchard analysis indicated that both an increase in Kd and a possible decrease in Bmax were responsible for the decrease in binding induced by low [Pb2+]f. Moreover, the effects of Pb2+ on the function of ER RyRs in neurons might also be controlled by other RyR modulators. Whole-cell patch-clamp experiments revealed that dynamic calcium oscillations evoked by specific RyR agonists were depressed rapidly and reversibly by exposure to 10μM Pb2+. Our study indicates that RyRs are molecular targets of Pb2+, and this interaction disturbs Ca2+ signals and leads to neurotoxicity.
Related Concept Videos
G-Protein Gated Ion Channels
Sensory...
Directly Acting Muscle Relaxants: Dantrolene and Botulinum Toxin
The binding of dantrolene to the RYR1...
Antihypertensive Drugs: Action of Calcium Channel Blockers
Feedback Regulation of Calcium Concentration
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...

