Characterization of ATP release, its fast actions on sensory neurons and their pharmacological modulation

ATP is a neurotransmitter at several sites in the central and peripheral nervous systems, particularly in pathways concerned with nociceptive input processing. This realization has prompted a number of studies to investigate how manipulating the action of ATP might lead to new forms of pain treatment. There is, however, a dearth of information about the mechanisms regulating the release of ATP in response to depolarization and how its effect on target neurons can be pharmacologically modulated. The present work was, therefore, focussed on two main aspects concerning the action of ATP. First, a new method, based on the use of PC12 cells in culture, was set up to investigate the characteristics of quantal release of endogenous ATP. Second, the characteristics of activation, desensitization and pharmacological modulation of the main class of ionotropic P2X3 receptors on sensory ganglia were studied. All these results were obtained with whole-cell patch clamping and calcium imaging experiments. PC12 cells contain ATP in dense core vesicles in which it is co-stored with catecholamines.