(±)3,4-methylenedioxyamphetamine inhibits the TEA-sensitive K⁺ current in the hippocampal neuron and the Kv2.1 current expressed in H1355 cells.
The whole-cell patch clamp method was used to study the effects of (±)3,4-methylenedioxyamphetamine (MDA) in hippocampal CA1 neurons from neonatal rats and in lung epithelial H1355 cells expressing Kv2.1. Extracellular application of MDA (30 μM) induced bursts of action potentials in hippocampal CA1 neurons exhibiting single spike action potentials without a bursting firing pattern, and promoted action potential bursts in hippocampal CA1 neurons exhibiting bursting firing of action potentials. Whereas MDA (30 and 100 μM) markedly decreased the delayed outward current in hippocampal CA1 neurons, MDA (100 μM) only slightly decreased the fast-inactivating K() current (I(A)) current. Furthermore, MDA (100 μM) substantially decreased the delayed outward current in the presence of 4-aminopyridine (4-AP 3 mM), but did not significantly decrease the delayed outward current in the presence of tetraethylammonium (TEA 30 mM). MDA (100 μM) also inhibited the current in H1355 cells expressing Kv2.1. Our results have shown that MDA inhibits the TEA-sensitive K() current in the hippocampus and the Kv2.1 current expressed in H1355 cells. These effects may contribute to the pharmacological and toxicological effects of MDA.