BIOCHEMICAL AND FUNCTIONAL-HETEROGENEITY OF RAT CEREBRUM MICROSOMAL-MEMBRANES IN RELATION TO SERCA CA2-ATPASES AND CA2+ RELEASE CHANNELS()

Rat cerebrum microsomes were subfractionated on isopycnic linear sucro se (20-42%) density gradients. The Ca2+ loading/release properties and the distribution of intracellular Ca2+ store channels, inositol 1,4,5 -trisphosphate (IP3) receptor and ryanodine (Ry) receptor, and SERCA p umps, were monitored in each subfraction by ligand binding and Ca-45(2 +) loading/release assays. Three different classes of vesicles were id entified: (i) heavy density vesicles with high content of Ry receptors and Ca2+ pumps and high thapsigargin (TG)-sensitivity of Ca2+ loading ; (ii) intermediate sucrose density vesicles with high content of IP3 receptor, high IP(S)(3) sensitivity of Ca2+ loading and low content of Ry receptors; and (iii) light sucrose density vesicles with high cont ent of Ry receptors, low content of IP3 receptors and low content of S ERCA pumps highly sensitive to TG. Isolation of molecularly heterogene ous rat cerebrum microsomes and identification of specific Ca2+ loadin g/release properties support the presence of multiple, potentially act ive, heterogeneous rapidly exchanging Ca2+ stores in rat cerebrum.