Margatoxin sensitive current regulates striatal cholinergic interneuron excitability

CECILIA TUBERT; GONZALO SANCHEZ; LORENA RELA; MARIO GUSTAVO MURER

Huerta Grande, Córdoba

Congreso; XXVIII Reunión Anual SAN; 2013

Sociedad Argentina de Investigación en Neurociencias

Acetylcholine and dopamine are the main modulators of corticostriatal function, and disbalances in their availability may result in neuropsychiatric disorders like Parkinson´s disease. Acetylcholine is released by striatal tonically active cholinergic interneurons (ChIs). Their tonic activity depends on intrinsic mechanisms. Recent work showed hyperactive ChIs in a rat model of Parkinson?s disease as a result of a lack of ?accommodation?. We study instrinsic properties of ChIs in mouse brain slices. Particularly, we try to identify the currents that regulate ChI excitability, using accommodation as an indicator. We used mice expressing the tdTomato fluorescent protein in ChIs (ChAT-Cre;rt) and made whole-cell recordings to study accommodation and the underlying current. We first validated the ChAT-Cre;rt model to be able to use it in the rest of the experiments. Our results show that margatoxin, a blocker of Kv channels with selectivity for Kv1.3 strongly reduced accommodation (p1500pA) in ChIs. Both were insensitive to UCL2077, a blocker of atypical KCNQ K+ channels. We have isolated and characterized the margatoxin sensitive current and found an activation voltage of -38+7mV and a V50 of -3+8mV. Immunohistochemistry revealed the presence of Kv1.3 channels. Our data suggest a novel voltage-dependent determinant of excitability in ChIs, which needs further validation as a therapeutic target in animal models of Parkinson?s disease.