Role of Kv1 Potassium Channels in Regulating Dopamine Release and Presynaptic D2 Receptor Function

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

Protective Agents in Parkinson's Disease: Caffeine and Adenosine A2A Receptor Antagonists

The pharmacologic management of Parkinson’s disease is based on drugs that act on the motor symptoms, whereas there are currently no drugs available that can alter the progressive neurodegeneration of dopaminergic neurons. Based on recent findings suggesting that the adenosinergic system is one of the most interesting in the field of neuroprotection in Parkinson’s disease, this chapter describes the functions of adenosine and its receptors in the central nervous system, with particular emphasis on their role in neurotoxicity/neuroprotection. Results of epidemiologic surveys demonstrating that intake of caffeine, an adenosine A1/A2A receptor antagonist, is inversely correlated with Parkinson’s disease are summarized. Moreover, evidence originating from preclinical studies showing that the antagonism of the adenosine A2A receptor is responsible for the neuroprotective effects of caffeine is also presented. This chapter therefore provides a comprehensive analysis of the current literature concerning the adenosinergic-based neuroprotective intervention strategy for Parkinson’s disease