Kv4 channel blockade reduces motor and neuropsychiatric symptoms in rodent models of Parkinson's disease. Issue 1 (February 2015)

• Record Type: Journal Article
• Authors: Aidi-knani, Sabrine; Regaya, Imed; Amalric, Marianne; Mourre, Christiane
• Is Part Of: Behavioural pharmacology. Volume 26:Issue 1/2(2015)
• Publication Date: 2015-02
• Subjects: anxiety -- A-type K current -- basal ganglia -- dopamine -- 6-hydroxydopamine -- memory -- nonmotor symptoms -- object recognition -- potassium voltage-dependent channels -- rat; Psychopharmacology -- Periodicals; Nervous System -- drug effects -- Periodicals; Behavior -- drug effects -- Periodicals; 615.78
• DOI: 10.1097/FBP.0000000000000107
• Languages: English
• ISSNs: 0955-8810

Abstract

Abstract : The striatum, a major input structure of basal ganglia, integrates glutamatergic cortical and thalamic inputs to control psychomotor behaviors. Nigrostriatal dopamine (DA) neurodegeneration in Parkinson's disease causes a loss of spinal and glutamatergic synapses in the striatal medium spiny neurons (MSNs). Adaptive responses, a form of homeostatic plasticity, to these changes are caused by a decrease in a potassium Kv4 channel-dependent inactivating A-type potassium (KIA ) current that increases the intrinsic excitability of MSNs. Nevertheless, the functional outcome of these compensatory mechanisms does not allow adequate behavioral recovery in vivo . We thus addressed the question of whether further blockade of Kv4 activity could enhance the striatal responsiveness of MSNs to DA depletion and restore normal function in vivo . To test this hypothesis, we examined the effects of a selective blocker of Kv4 channels, AmmTX3, on the motor, cognitive, and emotional symptoms produced by 6-hydroxydopamine lesions of the nigrostriatal DA pathway in rats. Striatal infusion of AmmTX3 (0.2–0.4 μg) reduced motor deficits, decreased anxiety, and restored short-term social and spatial memories. These results underlie the importance of Kv4 channels as players in the homeostatic responses, and, more importantly, provide a potential target for adjunctive therapies for Parkinson's disease.