Cross talk between Ca2+ and redox signalling cascades in muscle and neurons through the combined activation of ryanodine receptors/Ca2+ release channels.

Abstract

Calcium release mediated by the ryanodine receptors (RyR) Ca2+ release channels is required for muscle contraction and contributes to neuronal plasticity. In particular, Ca2+ activation of RyR-mediated Ca2+ release can amplify and propagate Ca2+ signals initially generated by Ca2+ entry into cells. Redox modulation of RyR function by a variety of non-physiological or endogenous redox molecules has been reported. The effects of RyR redox modification on Ca2+ release in skeletal muscle as well as the activation of signalling cascades and transcription factors in neurons will be reviewed here. Specifically, the different effects of S-nitrosylation or S-glutathionylation of RyR cysteines by endogenous redox-active agents on the properties of skeletal muscle RyRs will be discussed. Results will be presented indicating that these cysteine modifications change the activity of skeletal muscle RyRs, modify their behaviour towards both activators and inhibitors and affect their interactions with FKBP12 and calmodulin. In the hippocampus, sequential activation of ERK1/2 and CREB is a requisite for Ca2+-dependent gene expression associated with long-lasting synaptic plasticity. The effects of reactive oxygen/nitrogen species on RyR channels from neurons and RyR-mediated sequential activation of neuronal ERK1/2 and CREB produced by hydrogen peroxide and other stimuli will be discussed as well.