CHLORIDE CHANNEL BLOCK PHASE ADVANCES THE SINGLE-UNIT ACTIVITY RHYTHMIN THE SCN

The mammalian suprachiasmatic nuclei (SCN) contain a circadian pacemak er that exhibits a 24 h rhythm in single-unit activity in vivo and in vitro. Chloride channel block by a saturating concentration of picroto xin at either CT6 or CT15 produces large phase advances in the SCN sin gle-unit activity rhythm in vitro. These phase advances are not affect ed by simultaneous blockade of voltage-sensitive sodium and calcium ch annels by TTX and magnesium. Thus, the effects of picrotoxin appear to be mediated by direct blockade of the chloride channel, rather than s ubsequent membrane depolarization. GABA-A receptor-mediated chloride f lux may be part of the mechanism of circadian timekeeping.