Subcellular localization of Kv1.3 and Kv1.1 potassium channel subunits in striatal cholinergic interneurons of mouse models of experimental parkinsonism and L-DOPA-induced dyskinesia

JUAN BELFORTE; RODRIGO M PAZ; LORENA RELA; AGOSTINA M STAHL; MARIO GUSTAVO MURER

Córdoba

Congreso; XXXIII Congreso Anual; 2018

Sociedad Argentina de Investigación en Neurociencias

Parkinson's disease (PD) characterizes by a degeneration of mesencephalic dopaminergic neurons that innervate the striatum, a key nucleus for the selection of motor programs. In advanced stages of the disease only L-DOPA as a dopamine-replacement strategy allows an adequate performance in daily activities. However, the effectiveness of L-DOPA decreases and abnormal movements emerge (dyskinesia). Striatal cholinergic interneurons (SCIN) are key modulators of striatal circuits and are hyperexcitable in animal models of PD, owing to dysfunction of voltage-dependent potassium channels containing Kv1.3 and Kv1.1 subunits which is not due to a decrease in Kv1.3 protein expression. Enhanced SCIN activity was also linked to L-DOPA-induced dyskinesia (LID). Here we address whether SCIN dysfunction in mouse models of PD (unilateral lesion of the medial forebrain bundle with 6-OHDA) and LID is associated with an impaired trafficking of Kv1 channel subunits to the plasma membrane. We use genetically modified mice that express a fluorescent membrane marker (channelrhodopsin-EYFP fusion protein) in SCIN (ChAT-Cre;LSL-ChR2-EYFP) and analyze the distribution of the Kv1.3 and Kv1.1 subunits in the plasma membrane and intracellular compartments of SCIN, using immunohistochemistry. Preliminary results show that the fraction of Kv1.3 immunolabeling localized to the plasma membrane of SCIN in parkinsonian and dyskinetic mice did not differ from what was observed in unlesioned mice.