Functional coupling between ryanodine receptors and L-type calcium channels in neurons.
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.
Chavis
P
P
CNRS, U.P.R. 9023, C.C.I.P.E., Montpellier, France.
Fagni
L
L
Lansman
J B
JB
Bockaert
J
J
D000818:Animals; D001464:Barium / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel; D010738:Type C Phospholipases / Q000378:metabolism
D015220:Calcium Channels; D009124:Muscle Proteins; D010726:Phosphodiesterase Inhibitors; D018094:Receptors, Metabotropic Glutamate; D019837:Ryanodine Receptor Calcium Release Channel; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D012433:Ryanodine; D001464:Barium; D002110:Caffeine; D015544:Inositol 1,4,5-Trisphosphate; D011494:Protein Kinases; D010738:Type C Phospholipases