role of kv1 potassium channels in regulating dopamine release and presynaptic d2 receptor functionkv1钾离子通道的作用在调节多巴胺的释放和突触前d2受体功能.pdfVIP

Role of Kv1 Potassium Channels in Regulating Dopamine Release and Presynaptic D2 Receptor Function ´ Philippe Martel, Damiana Leo, Stephanie Fulton, Maxime Berard, Louis-Eric Trudeau* ` ´ ´ ´ ´ Department of Pharmacology, Faculty of Medicine, Groupe de Recherche sur le Systeme Nerveux Central, Universite de Montreal, Montreal, Quebec, Canada Abstract Dopamine (DA) release in the CNS is critical for motor control and motivated behaviors. Dysfunction of its regulation is thought to be implicated in drug abuse and in diseases such as schizophrenia and Parkinson’s. Although various potassium channels located in the somatodendritic compartment of DA neurons such as G-protein-gated inward rectifying potassium channels (GIRK) have been shown to regulate cell firing and DA release, little is presently known about the role of potassium channels localized in the axon terminals of these neurons. Here we used fast-scan cyclic voltammetry to study electrically- evoked DA release in rat dorsal striatal brain slices. We find that although G-protein-gated inward rectifying (GIRK) and ATP- gated (KATP) potassium channels play only a minor role, voltage-gated potassium channels of the Kv1 family play a major role in regulating DA release. The use of Kv subtype-selective blockers confirmed a role for Kv1.2, 1.3 and 1.6, but not Kv1.1, 3.1, 3.2, 3.4 and 4.2. Interestingly, Kv1 blockers also reduced the ability of quinpirole, a D2 receptor agonist, to inhibit evoked DA overflow, thus suggesting that Kv1 channels also regulate presynaptic D2 receptor function. Our work identifies Kv1 potassium channels as key regulators of DA release in the striatum.