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Inactivation of the sarcoplasmic reticulum calcium channel by protein kinase

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Abstract

THE ryanodine receptor protein of skeletal muscle sarcoplasmic reticulum (SR) membranes is a calcium ion channel which allows movement of calcium from the SR lumen into the cytoplasm during muscle activation1–5. Gating of this channel is modulated by a number of physiologically important substances including calcium. Interestingly, calcium has both activating and inactivating effects which are concentration- and tissue-specific. In skeletal muscle, calcium-dependent inactivation of calcium release occurs at concentrations reached physiologically, suggesting that calcium may modulate the release process by a negative feedback mechanism6–9. To determine the cellular mechanism responsible for calcium-dependent inactivation, we have investigated the ability of protein phosphorylation to affect single channel gating behaviour using the patch clamp technique. Here we demonstrate that the ryanodine receptor protein/calcium release channel of skeletal muscle SR is inactivated under conditions permissive for protein phosphorylation. This inactivation is reversed by the application of phosphatase and prevented by a peptide inhibitor specific for calcium/cal-modulin-dependent protein kinase II. The results provide evidence for an endogenous protein kinase which is closely associated with the ryanodine receptor protein and regulates channel gating.

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Authors and Affiliations

  1. Department of Physiology and Biophysics and the School of Medicine, University of Illinois, 524 Burrill Hall, 407 S. Goodwin Avenue, Urbana, Illinois, 61801, USA

    Jixin Wang & Philip M. Best

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  1. Jixin Wang
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  2. Philip M. Best
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Wang, J., Best, P. Inactivation of the sarcoplasmic reticulum calcium channel by protein kinase. Nature 359, 739–741 (1992). https://doi.org/10.1038/359739a0

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  • DOI: https://doi.org/10.1038/359739a0

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