The role of intravesicular ATP in excitatory and inhibitory synapses of the central nervous system
COST-ATP pretends to establish the role of intravesicular ATP in excitatory and inhibitory synapses of the central nervous system (CNS). Although, several laboratories have characterized the crucial interaction between ATP and catecholamines to permit its large accumulation in secretory vesicles of chromaffin cells, this crucial mechanism has not been studied in synaptic vesicles where high concentrations of neurotransmitters are needed for neuronal communication in the CNS. COST-ATP will combine the experience of the host laboratory in ATP as an accumulator of neurotransmitters in chromaffin cells and the TIRFM technology, and the ample experience of the researcher in cutting edge electrophysiological techniques in hippocampal neurons. The project will use electrophysiology, TIRFM, molecular biology and pharmacological tools to first discern the packagingbrole of vesicular ATP from its actions as neurotransmitter in central synapses using autaptic cultures of mouse hippocampal neurons. COST-ATP wants to explain why ATP is present inside of synaptic vesicles of almost all neurons. The mainadvantage of our approach is that we can modify the vesicular ATP by acting on the specific vesicular nucleotide carrier (VNUT) without affecting its cellular functions as the molecular energy. The consideration of the ATP, by its colligative properties, as a regulator of the neurotransmission, opens a new door in the neuronal communication. Given that its accumulation is mediated by VNUT a regulation of its activity could constitute a new pharmacological target for the treatment of neurological, psychiatric and cardiovascular diseases without involving membrane receptors.