Abstract：
:The present study investigated the membrane mechanisms underlying the inhibitory influence of melatonin on suprachiasmatic nucleus (SCN) neurones in a hypothalamic slice preparation. Perforated-patch recordings were performed to prevent the rapid rundown of spontaneous firing rate as observed during whole cell recordings and to preserve circadian rhythmicity in SCN neurones. In current-clamp mode melatonin (1 microM or 1 nM) application, in the presence of agents that block action potential generation and fast synaptic transmission, resulted in a membrane hyperpolarisation accompanied with a decrease in input resistance in the majority of SCN neurones (71-86%). The amplitude of the hyperpolarisation was not found to be significantly different between circadian time 5-12 and 14-21. In voltage-clamp mode melatonin (1 microM or 1 nM) induced an outward current accompanied with an increase in membrane conductance. The current was found to be mainly potassium driven with voltage kinetics resembling those of an open rectifying potassium conductance. Investigations into the signal transduction mechanism revealed melatonin-induced inhibition of SCN neurones to be sensitive to pertussis toxin but independent of intracellular cAMP levels and phospholipase C activity. The present study shows that melatonin, at night-time physiological concentrations, reduces the neuronal excitability of the majority of SCN neurones independent of the time of application in the circadian cycle. Thus in vivo melatonin may be important for circadian time-keeping by amplifying the circadian rhythm in SCN neurones, by lowering their sensitivity to phase-shifting stimuli occurring at night.
journal_name
Neurosciencejournal_title
Neuroscienceauthors
van den Top M,Buijs RM,Ruijter JM,Delagrange P,Spanswick D,Hermes MLdoi
10.1016/s0306-4522(01)00346-3keywords:
subject
Has Abstractpub_date
2001-01-01 00:00:00pages
99-108issue
1eissn
0306-4522issn
1873-7544pii
S0306-4522(01)00346-3journal_volume
107pub_type
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