PARTIAL CLONING AND DIFFERENTIAL EXPRESSION OF RYANODINE RECEPTOR CALCIUM-RELEASE CHANNEL GENES IN HUMAN TISSUES INCLUDING THE HIPPOCAMPUS AND CEREBELLUM

Cellular Ca2+ signalling is an important factor in the control of neur onal metabolism and electrical activity. Although the roles of Ca2+-re lease channels are well established for skeletal and cardiac muscle, l ess is known about their expression and roles in the central nervous s ystem, especially in the human brain. We have isolated partial complem entary DNAs derived from the human ryanodine receptor Ca2+-release cha nnel genes (ryr1, ryr2 and ryr3), and examined their expression in the human hippocampus and cerebellum. For comparison, we have included in our analysis an inositol trisphosphate Ca2+-release channel type I co mplementary RNA probe. All four messenger RNAs show widespread distrib ution in the human hippocampus, where ryr2 is the most abundant isofor m, and all four are expressed in the human cerebellum. However, striki ng differences were seen between ryr and inositol trisphosphate Ca2+-r elease channel type I complementary RNA expression in the cerebellum, with inositol trisphosphate Ca2+-release channel type I messenger RNA being largely restricted to, and very highly expressed, in Purkinje ce lls, whereas ryr1, ryr2 and ryr3 were all expressed predominantly in t he granular layer. The widespread expression of ryr isoforms in the hu man hippocampus and cerebellum suggests that ryanodine receptor protei ns may have a central role in Ca2+ signalling and Ca2+ homeostasis in the human central nervous system. These may include roles in fundament al processes like synaptic plasticity. Furthermore, these Ca2+-release channels may be involved in pathogenic processes such as excitotoxici ty, where excessive rises in intracellular Ca2+ concentration mediate neuronal cell death. (C) 1998 IBRO. Published by Elsevier Science Ltd.