Melatonin inhibits outward delayed rectifier potassium currents in hippocampal CA1 pyramidal neuron via intracellular indole-related domains

In the present study, we investigated the effect of melatonin on the outward delayed rectifier potassium currents (I-K) in CA1 pyramidal neurons of rat hippocampal slices using patch-clamp technique in whole-cell configuration. In a concentration-dependent manner, melatonin caused a reduction of I-K with a half-maximal inhibitory concentration (IC50) of 3.75 mm. The inhibitory effect had rapid onset and was readily reversible. Melatonin shifted steady-state inactivation of I-K in hyperpolarizing direction but did not alter its steady-state activation. Neither luzindole, an MT1/MT2 receptor antagonist, nor prazosin, an MT3 receptor antagonist, blocked melatonin-induced current reduction. The results indicate that melatonin-induced I-K inhibition was not via activation of its own membrane receptors. 5-Hydroxytryptamine (5-HT), a melatonin precursor and an agonist of serotonin receptors, when it was given in pipette internal solution but not bath solution, produced a similar inhibitory effect to that of melatonin. Moreover, indole, a major component of melatonin, reversibly and dose dependently inhibited I-K with an IC50 of 3.44 mm. Present results suggest that melatonin inhibits I-K in hippocampal CA1 pyramidal neurons probably through its interaction with the intracellular indole-related domains of potassium channels.