Summary

The release of stored Ca2+ from intracellular pools trig-gers a variety of important neuronal processes. Physio-logical and pharmacological evidence has indicated the presence of caffeine-sensitive intracellular pools that are distinct from the well-characterized inositol 1,4,5,-tris-phosphate (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 recep-tor has been purified 6700-fold with no change in [3H]ry-anodine binding affinity and shown to be a homotetra-mer composed of an approximately 500 kd protein subunit, which is identified by anti-peptide antibodies against the skeletal and cardiac muscle ryanodine recep-tors. Our results demonstrate that the brain ryanodine receptor functions as a caffeine-sensitive Ca2+ release channel and thus is the likely gating mechanism for intra-cellular caffeine-sensitive Ca2+ pools in neurons