Thyroid hormones reduce nicotinic receptor mediated currents in SH-SY5Y neuroblastoma cells.

Abstract

Thyroid hormones (THs) are crucial for maturation and functioning of mammalian CNS. THs "classical" signaling involves nuclear receptors binding but alsotheir non genomic actions, as rapid modulators of cell activity, are widely recognized. Since THs imbalance affects cognition and the cholinergic system is deeply involved in learning and memory processes we have studied THs effects at the level of the nicotinic acetylcholine receptors (nAchR). We used the patch-clamp technique to analyze T3 and T4 modulation of nicotine (NIC)-mediated current in SH-SY5Y neuroblastoma cells. Both hormones decreased NIC-evoked current in a dose dependent fashion. The antagonism was reversible, not competitive and not blocked by Tetrac, an integrin αVβ3 receptor antagonist. A similar effect was detected with the endogenous agonist Acetylcholine. THs potencies were higher at 100μM NIC (IC50 = 4.6 ± 2μM for T3 and 4.8 ± 2μM for T4) compared to those measured at 10μM NIC (IC50 = 10 ± 4μM for T3 and 8 ± 4μM for T4). Furthermore, the efficacy of THs reached almost 90% at 100μM NIC while was about 30 % at 10μM NIC. THs inhibited nAchR-mediated currents by enhancing receptor desensitization and this effect was more pronounced at high agonist concentrations. Our results make light on a new non genomic activity of THs at the level of nAchR. This mechanism of action of THs can provide a new explanation for the cognitive deficitsassociated with tyroid dysfunction.