A vital role for voltage-dependent potassium channels in dopamine transporter-mediated 6-hydroxydopamine neurotoxicity.

摘要: 6-Hydroxydopamine (6-OHDA), a neurotoxic substrate of the dopamine transporter (DAT), is widely used in Parkinson's disease models. However, molecular mechanisms underlying 6-OHDA's selectivity for neurons and injurious sequelae that it triggers are not well understood. We tested whether ectopic expression DAT induces sensitivity to 6-OHDA non-dopaminergic rat cortical evaluated contribution voltage-dependent potassium channel (Kv)-dependent apoptosis toxicity this compound midbrain neurons. Cortical expressing accumulated were highly vulnerable 6-OHDA. Pharmacological inhibition completely blocked toxicity. also observed p38-dependent Kv current surge DAT-expressing exposed 6-OHDA, p38 antagonists blockers neuroprotective model. Thus, DAT-mediated uptake recruited oxidant-induced dependent cell death pathway present Finally, we report increased currents cultured was with antagonists. conclude native accounts neuron specific Following uptake, oxidant-associated channel-dependent conserved