Increasing external K+ blocks phase shifts in a circadian rhythm produced by serotonin or 8-benzylthio-cAMP.
Serotonin (5-HT) phase shifts the circadian rhythm from the isolated eye of Aplysia. The discovery of the mechanisms involved in phase shifting by 5-HT may help elucidate the nature of the circadian oscillator. We have found that 5-HT appears to phase shift by causing a change in membrane K+ conductance. Solutions containing zero K+(0-K+) phase shift the rhythm and the phase response curve (PRC) for 0-K+ is similar to one previously obtained for 5-HT. The similarity in PRCs for 0-K+ and 5-HT suggested that these treatments may be phase shifting the rhythm through a common mechanism. The nonadditivity of phase shifting by 0-K+ and 5-HT supports this suggestion. A common mechanism of action of 5-HT and 0-K+ might be effects on membrane potentials. The possible involvement of a membrane potential change in mediating the effect of 5-HT and the lack of an effect of large reductions in Na+, Cl-, and Ca2+ ions on phase shifting by 5-HT led us to examine the role of K+ ions in phase shifting by 5-HT. A change in K+ conductance may mediate the effects of 5-HT on the rhythm because HiK (30mM) solutions blocked the phase shift normally produced by 5-HT. The conductance change produced by 5-HT may be an increase in K+ conductance which would produce a hyperpolarization and not a decrease in K+ conductance which would produce a depolarization since depolarizing treatments, HiK (30-110mM), had no effect on the rhythm at the phase where 5-HT produces its largest phase shifts. Since we previously found that the effects of 5-HT appear to be mediated by cAMP, we examined whether HiK solutions could block the effects of 8-benzylthio-cAMP on the rhythm. HiK (40mM) blocked the phase shifts normally produced by 8-benylthio-cAMP. Our working hypothesis for the 5-HT phase-shifting pathway based on these results is 5-HT leads to increased cAMP leads to elevates K+ conductance leads to membrane hyperpolarization leads to phase shifts the rhythm.
D000818:Animals; D001048:Aplysia / Q000502:physiology*; D001696:Biomechanical Phenomena; D002940:Circadian Rhythm / Q000187:drug effects*; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004553:Electric Conductivity; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology*
C024322:8-thio-benzyl cyclic AMP; D012701:Serotonin; D000242:Cyclic AMP; D011188:Potassium