Melatonin activates an outward current and inhibits Ih in rat suprachiasmatic nucleus neurons.
Whole-cell voltage-clamp recordings were made from suprachiasmatic nucleus (SCN) neurons maintained in horizontal brain slices. The majority of neurons exhibited spontaneous and evoked excitatory and inhibitory synaptic currents (EPSC and IPSC), mediated by glutamate and GABA respectively. Melatonin had no effect on either the spontaneous or evoked EPSC or IPSC. Application of melatonin (0.1-30 microM) during circadian time (CT) 9-12 activated an outward current at -60 mV and increased the membrane conductance in a concentration-dependent manner. The current was augmented by depolarization, reduced by hyperpolarization and, in some cells, reversed its polarity near the potassium equilibrium potential. Some neurons also responded to melatonin during other times of the circadian day (CT 3-9 or CT 12-15). Hyperpolarizing steps, in a portion of cells, activated an inward cation current which resembled the Ih described in other neurons. Melatonin (10 microM) inhibited activation of the Ih. These data indicate that melatonin may inhibit SCN neurons by activating a potassium current and inhibiting the Ih.
Jiang
Z G
ZG
Center for Research on Occupational and Environmental Toxicology, Oregon Health Sciences University, Portland 97201-3098, USA.
Nelson
C S
CS
Allen
C N
CN
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002586:Cesium / Q000494:pharmacology; D002940:Circadian Rhythm / Q000187:drug effects; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D007473:Ion Channels; D015221:Potassium Channels; D002586:Cesium; D001464:Barium; D008550:Melatonin