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(±)3,4-methylenedioxyamphetamine inhibits the TEA-sensitive K⁺ current in the hippocampal neuron and the Kv2.1 current expressed in H1355 cells.

Chia-Hsien Lin, Chin-Tsang Yang, Ming-Cheng Tsai, Ya-Ting Wu, Iona MacDonald, Mei-Ling Wang, Chien-Hua Wu, Yuk-Man Leung, Yi-Hung Chen

Neuropharmacology February 2015 DOI: 10.1016/j.neuropharm.2014.09.009 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Laboratory experimental study Peer reviewed
Population Hippocampal CA1 neurons from neonatal rats and lung epithelial H1355 cells expressing Kv2.1
Intervention MDA
Dose 30 μM, 100 μM
Keywords ±3,4-methylenedioxyamphetamine Action potentials Hippocampal neuron K+ current
Key findings MDA (30 μM) induced or promoted bursts of action potentials in hippocampal CA1 neurons and, at 30 and 100 μM, markedly decreased the delayed outward potassium current, with only a slight effect on the fast-inactivating current. The delayed current reduction occurred with 4-aminopyridine present but not with tetraethylammonium, and MDA (100 μM) also inhibited Kv2.1 current in H1355 cells, suggesting MDA acts on a TEA-sensitive potassium current.

Abstract

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.

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