The ryanodine receptors Ca2+ release channels: cellular redox sensors?
The release of Ca2+ from intracellular stores mediated by ryanodine receptors (RyR) Ca2+ release channels is essential for striated muscle contraction and contributes to diverse neuronal functions including synaptic plasticity. Through Ca2+-induced Ca2+-release, RyR can amplify and propagate Ca2+ signals initially generated by Ca2+ entry into cardiac muscle cells or neurons. In contrast, RyR activation in skeletal muscle is under membrane potential control and does not require Ca2+ entry. Non-physiological or endogenous redox molecules can change RyR function via modification of a few RyR cysteine residues. This critical review will address the functional effects of RyR redox modification on Ca2+ release in skeletal muscle and cardiac muscle as well as in the activation of signaling cascades and transcriptional regulators required for synaptic plasticity in neurons. Specifically, the effects of endogenous redox-active agents, which induce S-nitrosylation or S-glutathionylation of particular channel cysteine residues, on the properties of muscle RyRs will be discussed. The effects of endogenous redox RyR modifications on cardiac preconditioning will be analyzed as well. In the hippocampus, sequential activation of ERKs and CREB is a requisite for Ca2+-dependent gene expression associated with long lasting synaptic plasticity. Results showing that reactive oxygen/nitrogen species modify RyR channels from neurons and the RyR-mediated sequential activation of neuronal ERKs and CREB produced by hydrogen peroxide and other stimuli will be also discussed.
Hidalgo
Cecilia
C
FONDAP Center of Molecular Studies of the Cell, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile. chidalgo@med.u-chile.cl
Donoso
Paulina
P
Carrasco
M Angélica
MA
D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials; D018482:Muscle, Skeletal / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010084:Oxidation-Reduction; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction
D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium