Functional coupling between ryanodine receptors and L-type calcium channels in neurons

Nature. 1996 Aug 22;382(6593):719-22. doi: 10.1038/382719a0.


In skeletal muscle, L-type Ca2+ channels act as voltage sensors to control ryanodine-sensitive Ca2+ channels in the sarcoplasmic reticulum. It has recently been demonstrated that these ryanodine receptors generate a retrograde signal that modifies L-type Ca2+ -channel activity. Here we demonstrate a tight functional coupling between ryanodine receptors and L-type Ca2+ channel in neurons. In cerebellar granule cells, activation of the type-1 metabotropic glutamate receptor (mGluR1) induced a large, oscillating increase of the L-type Ba2+ current. Activation occurred independently of inositol 1,4,5-trisphosphate and classical protein kinases, but was mimicked by caffeine and blocked by ryanodine. The kinetics of this blockade were dependent on the frequency of Ba2+ current stimulation. Both mGluR1 and caffeine-induced increase in L-type Ca2+ -channel activity persisted in inside-out membrane patches. In these excised patches, ryanodine suppressed both the mGluR1- and caffeine-activated L-type Ca2+ channels. These results demonstrate a novel mechanism for Ca2+ -channel modulation in neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Barium / metabolism
  • Caffeine / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism*
  • Cells, Cultured
  • Cerebellum / cytology
  • Cycloleucine / analogs & derivatives
  • Cycloleucine / pharmacology
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Membrane Potentials
  • Mice
  • Muscle Proteins / drug effects
  • Muscle Proteins / metabolism*
  • Neurons / metabolism*
  • Phosphodiesterase Inhibitors / pharmacology
  • Protein Kinases / metabolism
  • Receptors, Metabotropic Glutamate / metabolism
  • Ryanodine / pharmacology
  • Ryanodine Receptor Calcium Release Channel
  • Type C Phospholipases / metabolism


  • Calcium Channels
  • Muscle Proteins
  • Phosphodiesterase Inhibitors
  • Receptors, Metabotropic Glutamate
  • Ryanodine Receptor Calcium Release Channel
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • Ryanodine
  • Barium
  • Caffeine
  • Inositol 1,4,5-Trisphosphate
  • Protein Kinases
  • Type C Phospholipases