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Inactivation of the sarcoplasmic reticulum calcium channel by protein kinase

Nature volume 359, pages 739–741 (1992)Cite this article

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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