Purinergic regulation of the synaptic activity by non-vesicular endogenous ATP the mouse neuromuscular junction

HURTADO PASO, MAXIMILIANO; GALIZIA, LUCIANO; GUARRACINO, JUAN; FRONTERA, TAMARA; LOSAVIO, ADRIANA

Mar del Plata

Congreso; LXIV Reunión Sociedad Argentina de Investigación Clínica; 2019

Sociedad Argentina de Investigación Clínica

At mammalian neuromuscular junction, ATP is co-released with theneurotransmitter ACh and once in the synaptic cleft it ismetabolized via ecto-nucleotidases to adenosine. Previous reportsof our laboratory have demonstrated that both purines modulateACh release when activating presynaptic inhibitory P2Y13(Guarracino et al 2016, 2018), A1 (De Lorenzo et al 2004) and A3receptors (Cinalli et al 2013) and facilitatory A2A receptors (Palmaet al 2011). It is accepted that the major source of purines in thesynaptic cleft is vesicular ATP (Redman & Silinsky 1994). However,there is evidence that at least half of the nerve-evoked release ofATP is derived from activated muscle fibers (Santos et al., 2003;Smith, 1991). It was recently proposed that ATP can be secretedfrom skeletal muscle fibers through pannexins located in the Ttubules (Riquelme et al 2013). Considering that high K+concentration increases the activity of pannexins, the aim of thiswork was to evaluate whether the ATP released from muscle fibersvia pannexins contribute to the purinergic modulation ofneurotransmitter secretion when membranes are depolarized byincreasing K+ concentrations