FUNCTIONALLY HETEROGENOUS RYANODINE RECEPTORS IN AVIAN CEREBELLUM

The functional heterogeneity of the ryanodine receptor (RyR) channels in avian cerebellum was defined, Heavy endoplasmic reticulum microsome s had significant levels of ryanodine and inositol 1,4,5-trisphosphate binding. Scatchard analysis and kinetic studies indicated the existen ce of at least two distinct ryanodine binding sites, Ryanodine binding was calcium-dependent but was not significantly enhanced by caffeine, Incorporation of microsomes into planar lipid bilayers revealed ion c hannels with pharmacological features (calcium, magnesium, ATP, and ca ffeine sensitivity) similar to the RyR channels found in mammalian str iated muscle, Despite a wide range of unitary conductances (220-500 pi cosiemens, symmetrical cesium methanesulfonate), ryanodine locked both channels into a characteristic slow gating subconductance state, posi tively identifying them as RyR channels. Two populations of avian RyR channels were functionally distinguished by single channel calcium sen sitivity, One population was defined by a bell-shaped calcium sensitiv ity analogous to the skeletal muscle RyR isoform (type I). The calcium sensitivity of the second RyR population was sigmoidal and analogous to the cardiac muscle RyR isoform (type II), These data show that ther e are at least two functionally distinct RyR channel populations in av ian cerebellum, This leads to the possibility that these functionally distinct RyR channels are involved in different intracellular calcium signaling pathways.