Inactivation of the sarcoplasmic reticulum calcium channel by protein kinase

Nature. 1992 Oct 22;359(6397):739-41. doi: 10.1038/359739a0.

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 activation. 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 mechanism. 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/calmodulin-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Calcium / metabolism
  • Calcium Channels / metabolism*
  • Calcium-Calmodulin-Dependent Protein Kinases
  • In Vitro Techniques
  • Ion Channel Gating / drug effects
  • Phosphoprotein Phosphatases / metabolism
  • Protein Kinase Inhibitors
  • Protein Kinases / metabolism*
  • Ranidae
  • Receptors, Cholinergic / metabolism*
  • Ryanodine Receptor Calcium Release Channel
  • Sarcoplasmic Reticulum / metabolism*
  • Signal Transduction

Substances

  • Calcium Channels
  • Protein Kinase Inhibitors
  • Receptors, Cholinergic
  • Ryanodine Receptor Calcium Release Channel
  • Adenosine Triphosphate
  • Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Phosphoprotein Phosphatases
  • Calcium