P/Q-type calcium channel á1 subunit is necessary for ALS-IGGS

VATTINO LUCAS; GONZALEZ LAURA E; KOTLER MÓNICA; REISIN RICARDO; UCHITEL OSVALDO

Huerta Grande, Córdoba, Argentina

Congreso; II Reunion Conjunta de Neurociencias (IIRCN); 2010

Sociedad Argentina de Neurociencias

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that promo¡©tes motoneurons¢¥ dysfunction and death. Most patients present a sporadic form of unknown etiology. In spite of the existence of many hypotheses trying to explain this variant, there is ample evidence supporting immune-mediated mechanisms. The aim of our work was to evaluate whether the absence of the ¥á1A subunit could affect the neuromuscular junction (NMJ) spontaneous synaptic activity modula¡©tion already observed with IgGs from our patients (ALS-IgGs). Electrophysiologi¡©cal experiments on mouse diaphragm were performed by intracellular recordings while immunofluorescence assays were carried out using ALS-IgGs as primary antibodies. We found that 63% of our ALS-IgGs (5/8) were able to significantly increase miniature end-plate potentials (MEPPs) frequencies and presented a strong immunoreactivity against NMJ. In addition, using ¥á1A+/+ and ¥á1A-/- mice, we discovered a positive correlation between ALS-IgGs effects and the presence of P/Q-type voltage-dependent calcium channels (VDCCs). We found a significant decrease in NMJ immunoreactivity in ¥á1A-deficient animals as well as a lack of ALS-IgGs effects over MEPPs frequencies. We concluded that the absence of the P/Q-type VDCC, or at least its ¥á1 subunit, was positively correlated with synaptic modulation activity in ALS IgGs samples.