Melatonin inhibits nicotinic currents in cultured rat cerebellar granule neurons

There is limited data regarding the effects of melatonin on the activity of neuronal acetylcholine receptors (nAChRs) themselves. This study analyzes the effects of low concentrations of melatonin on nicotine-evoked currents from cerebellar granule neurons (CGNs) in culture. Using electrophysiological and Ca(2+)-imaging techniques, it was found a subset of rat CGNs to which nicotine application elicited both intracellular Ca(2+) transients and inward whole-cell currents. These responses were mediated by heteromeric nAChRs, as assessed by their sensitivity to nicotine and time constant of current decay. Preincubating the cells with low melatonin concentrations (down to 1 pm) significantly reduced the current amplitude in a dose-dependent manner, without affecting the receptor's apparent affinity and voltage-dependency, nor the current's rise and decay time course. The inhibitory effect of melatonin was significantly reduced by luzindole, a competitive antagonist of both MT(1) and MT(2) melatonin receptors. In conclusion, melatonin inhibits nicotinic currents through non-alpha7 heteromeric nAChRs expressed by CGNs in culture, an effect that appears to be at least partially mediated by melatonin membrane receptors. Direct modulation of nicotinic receptors is accomplished at doses that are likely to be physiologically relevant, thus providing a mechanism through which melatonin circadian rhythmic levels could modulate cholinergic activity.