P32.-Array Tomography as a Tool for Tracking the Distribution of ASIC1a at the Neuromuscular Junction

LINO NG; URBANO FJ; UCHITEL OD

HUERTA GRANDE, CORDOBA ARGENTINA

Congreso; XXIX ANNUAL MEETING AND SAN-ISN SMALL COFERENCE AND COURSE; 2014

SOCIEDAD ARGENTINA DE INVESTIGACIÓN EN NEUROCIENCIAS

The maintenance of the extracellular pH proves to be critical for ensuring normal cellular function. At the presynaptic terminal of neuromuscular junctions (NMJs) H+ are co-released with acetylcholine and pumped in and out of the synaptic cleft after prolonged stimulation. Interesting candidates for sensing H+ are acid-sensing ion channels (ASICs). ASICs are voltage-independent cation-permeable ion channels, activated by extracellular acidosis. In this regard, we have shown that ASIC1a inhibits synaptic transmission during high frequency stimulation in female mice, which prompted us to hypothesize that ASIC1a may be involved in preventing muscle weakness after repetitive tetanic contraction and helping recovering neuromuscular transmission after muscle acidosis. Besides, by basic immunohistochemistry we have observed that ASIC1a seems to be located at the presynaptic terminal. However, another technique, by which we would be able to describe more accurately the distribution of ASIC1a at the NMJ and identify possible interactions with other presynaptic proteins, needed to be found. For that purpose, we took advantage of array tomography, a new imaging method which combines and extends superlative features of modern optical fluorescence and electron microscopy methods. Our results showed that, contrary to what had been suggested, ASIC1a may be located in Schwann cells, which lead us to rethink the mechanism by which ASIC1a exerts its modulatory role on synaptic transmission.