Ryanodine receptor Ca2+-release channels are an output pathway for the circadian clock in the rat suprachiasmatic nuclei

Ryanodine-sensitive intracellular Ca2+ channels (RyRs) are present in suprachiasmatic nuclei (SCN) neurons, but the functions served by these channels are not known. Here we addressed whether mobilization of intracellular Ca2+ stores through the RyRs may be a link between the molecular clock and the firing rate in SCN neurons. Activation of the RyRs by administration of either 1 mM caffeine or 100 nM ryanodine increased the firing frequency, whereas inhibition of RyRs by 10 mu M dantrolene or 80 mu M ryanodine decreased firing rate. Similar results were obtained in experiments conducted at either midday or midnight. Furthermore, these effects were not mediated by synaptic transmission as blockade of GABA A, AMPA and NMDA receptors did not prevent the excitatory or inhibitory effects induced by either dose of ryanodine on SCN firing. We conclude that gating of RyRs is a key element of the intricate output pathway from the circadian clock within SCN neurons in rats.