Chloride channel block phase advances the single-unit activity rhythm in the SCN.
The mammalian suprachiasmatic nuclei (SCN) contain a circadian pacemaker that exhibits a 24 h rhythm in single-unit activity in vivo and in vitro. Chloride channel block by a saturating concentration of picrotoxin at either CT6 or CT15 produces large phase advances in the SCN single-unit activity rhythm in vitro. These phase advances are not affected by simultaneous blockade of voltage-sensitive sodium and calcium channels by TTX and magnesium. Thus, the effects of picrotoxin appear to be mediated by direct blockade of the chloride channel, rather than subsequent membrane depolarization. GABA-A receptor-mediated chloride flux may be part of the mechanism of circadian timekeeping.
Rangarajan
R
R
Department of Biological Sciences, Stanford University, CA 94305.
Heller
H C
HC
Miller
J D
JD
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D002940:Circadian Rhythm / Q000187:drug effects; D015636:Magnesium Chloride / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000502:physiology*; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013493:Suprachiasmatic Nucleus / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D018118:Chloride Channels; D015636:Magnesium Chloride; D010852:Picrotoxin; D013779:Tetrodotoxin