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

STAHL, AGOSTINA; PAZ, RODRIGO MANUEL; TUBERT, CECILIA; BELFORTE, J.E.; MURER MG; RELA, LORENA

cordoba

Conferencia; XXXIII CONGRESO ANUAL SAN 2018; 2018

Sociedad Argentina de Investigacón en Neurociencias

Parkinson's disease (PD) characterizes by a degeneration of mesencephalic dopaminergic neuronsthat innervate the striatum, a key nucleus for the selection of motor programs. In advanced stagesof the disease only L DOPA as a dopamine replacement strategy allows an adequate pe rformancein daily activities. However, the effectiveness of L DOPA decreases and abnormal movementsemerge (dyskinesia). Striatal cholinergic interneurons (SCIN) are key modulators of striatal circuitsand are hyperexcitable in animal models of PD, owing to dysfunction of voltage dependentpotassium channels containing Kv1.3 and Kv1.1 subunits which is not due to a decrease in Kv1.3protein expression. Enhanced SCIN activity was also linked to L DOPA induced dyskinesia (LID).Here we address whether SCIN d ysfunction in mouse models of PD (unilateral lesion of the medialforebrain bundle with 6 OHDA) and LID is associated with an impaired trafficking of Kv1 channelsubunits to the plasma membrane. We use genetically modified mice that express a fluorescentm embrane marker (channelrhodopsin EYFP fusion protein) in SCIN (ChAT Cre;LSL ChR2 EYFP) andanalyze the distribution of the Kv1.3 and Kv1.1 subunits in the plasma membrane and intracellularcompartments of SCIN, using immunohistochemistry. Preliminary resul ts show that the fraction ofKv1.3 and Kv1.1 immunolabeling localized to the plasma membrane of SCIN in parkinsonian anddyskinetic mice did not differ from what was observed in unlesioned mice.