Control of excitability in striatal cholinergic interneurons: mechanism underlying IsAHP

CECILIA TUBERT; GONZALO SANCHEZ; GUSTAVO MURER; LORENA RELA

Huerta Grande, Córdoba

Congreso; XXVII Congreso Anual de la SAN; 2012

SAN - Sociedad Argentina de Neurociencias

Parkinson?s disease is a neurodegenerative disorder caused by nigrostriatal dopaminergic neuron loss. Acetylcholine released by a small population of tonically active interneurons (ChIs), is a main modulator of striatal function. Tonic activity in ChIs depends on intrinsic mechanisms. Action potentials open K+ channels, either KCa or Kv, leading to an afterhyperpolarization (AHP) with three phases: fAHP, mAHP, and sAHP. Molecular mechanisms that mediate IsAHP in ChIs are still unknown, but it is supposed to be Ca2+ dependent. Previous work shows that a reduction of IsAHP results in hyperactive ChIs in a rat model of Parkinson?s disease, which is seen as a lack of ?accommodation?. Thus, IsAHP may be a novel target to treat the hypercholinergic state in Parkinson?s disease. Here we study the maturation and pharmacology of IsAHP in ChIs from mouse brain slices. Accommodation and IsAHP in ChIs were insensitive to UCL2077, a blocker of atypical KCNQ K+ channels, but they were strongly reduced by margatoxin, a blocker of voltage-gated K+ channels with selectivity for Kv1.3 channels. Thus, our data suggest a novel voltage-dependent component of IsAHP in ChIs which needs further validation as a therapeutic target in animal models of Parkinson?s disease.