The brain ryanodine receptor: a caffeine-sensitive calcium release channel.
The release of stored Ca2+ from intracellular pools triggers a variety of important neuronal processes. Physiological and pharmacological evidence has indicated the presence of caffeine-sensitive intracellular pools that are distinct from the well-characterized inositol 1,4,5,-trisphosphate (IP3)-gated pools. Here we report that the brain ryanodine receptor functions as a caffeine- and ryanodine-sensitive Ca2+ release channel that is distinct from the brain IP3 receptor. The brain ryanodine receptor has been purified 6700-fold with no change in [3H]ryanodine binding affinity and shown to be a homotetramer composed of an approximately 500 kd protein subunit, which is identified by anti-peptide antibodies against the skeletal and cardiac muscle ryanodine receptors. Our results demonstrate that the brain ryanodine receptor functions as a caffeine-sensitive Ca2+ release channel and thus is the likely gating mechanism for intracellular caffeine-sensitive Ca2+ pools in neurons.
McPherson
P S
PS
Program in Neuroscience, University of Iowa College of Medicine, Iowa City 52242.
Kim
Y K
YK
Valdivia
H
H
Knudson
C M
CM
Takekura
H
H
Franzini-Armstrong
C
C
Coronado
R
R
Campbell
K P
KP
D000818:Animals; D001703:Biophysics / Q000379:methods; D001921:Brain / Q000378:metabolism*; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates / Q000378:metabolism; D008051:Lipid Bilayers; D008854:Microscopy, Electron / Q000379:methods; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000302:isolation & purification; D011950:Receptors, Cholinergic / Q000302:isolation & purification / Q000502:physiology* / Q000648:ultrastructure; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates; D008051:Lipid Bilayers; D011956:Receptors, Cell Surface; D011950:Receptors, Cholinergic; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; D002110:Caffeine; D002118:Calcium