Juan Jose Garrido Jurado

Recently, changes in the axon initial segment (AIS) integrity have been related to neuropsychiatric/neurodegenerative diseases and brain injury. The axon initial segment (AIS) is the place of action potential generation, mediated by a high concentration of voltage gated sodium, potassium and calcium channels. The activation of these channels can be modulated, and in fact, purinergic receptors have been proposed as intermediate regulators of voltage gated potassium and calcium channels. Recent results from our laboratory in cultured hippocampal neurons show that ATP gated P2X7 receptor antagonists impair alterations at the AIS caused by a high extracellular ATP concentration, such as those achieved after brain injury. The P2X7 receptor signalling pathway includes calcium entry and the regulation of GSK3 activity, the later being involved in determining sodium channel functional expression at the AIS (Garrido and Debanne laboratories, submitted, see CV). The aim of this collaborative project is to study the involvement of P2X7 in the functional expression of ionic channels at the AIS and the regulation of neuronal excitability in rat brain slices using electrophysiological techniques in the laboratory of Dr. Dominique Debanne as a continuation of a previous collaboration. In parallel, we pretend to analyze how potassium channels, such as Kv1.1, paraticipates in the functional and structural maturation of the AIS.