ryanodine and Cadaver

The pharmacological properties, regional distribution and autoradiographic localization of [3H]ryanodine binding sites were examined in postmortem human brain. Analyses of binding data from labeled ryanodine titration experiments conducted in frontal cortex revealed a single class of high affinity binding sites with a Kd value of 3.6 nM and a Bmax value of 99 fmol/mg protein. In unlabeled ryanodine titration experiments, Kd and Bmax values were 6.5 nM and 132 fmol/mg protein, respectively. Binding was found to be dependent on free Ca2+ (ED50 value, 89 microM) and was decreased by 35% in the presence of 5 mM Mg2+. This Mg2+ inhibition was abolished by the addition of 10 mM caffeine. Analysis of the regional distribution of [3H]ryanodine binding in membrane preparations revealed high levels of sites in putamen and caudate nucleus, intermediate levels in hippocampus and cortex, and low levels in cerebellum. Autoradiographically, the hippocampus displayed a high density of binding sites in the CA3 region and the dentate gyrus. Ryanodine binding sites in human brain exhibit similar, but not identical binding and pharmacological characteristics to ryanodine receptors previously identified in muscle and more recently in rat and rabbit brain and accordingly may be involved in the regulation of intracellular calcium.

Topics: Aged; Autoradiography; Binding Sites; Binding, Competitive; Brain; Cadaver; Caffeine; Calcium; Female; Humans; Magnesium; Male; Middle Aged; Ryanodine; Tissue Distribution; Tritium