Increasing external K+ blocks phase shifts in a circadian rhythm produced by serotonin or 8‐benzylthio‐cAMP

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Abstract
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+ (O‐K+) phase shift the rhythm and the phase response curve (PRC) for O‐K+ is similar to one previously obtained for 5‐HT. The similarity in PRCs for O‐K+ and 5‐HT suggested that these treatments may be phase shifting the rhythm through a common mechanism. The nonadditivity of phase shifting by O‐K+ and 5‐HT supports this suggestion. A common mechanism of action of 5‐HT and O‐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 rhthym 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 treatment, 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‐benzylthio‐cAMP. Our working hypothesis for the 5‐HT phase‐shifting pathway based on these results is 5‐HT → increased cAMP → elevates K+ conductance → membrane hyperpolarization → phase shifts the rhythm.