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 microM dantrolene or 80 microm 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.
Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apdo. Postal 70-253, México D.F. 04510, Mexico. raguilar@ifc.unam.mx
Raúl
R
Aguilar-Roblero
Clara
C
Mercado
Javier
J
Alamilla
Antonio
A
Laville
Mauricio
M
Díaz-Muñoz
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002110:Caffeine / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D003620:Dantrolene / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008297:Male; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D009125:Muscle Relaxants, Central; D010726:Phosphodiesterase Inhibitors; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D002110:Caffeine; D003620:Dantrolene