Price, Gareth David; (2002) The role of P2 receptors in fast synaptic transmission in the rat medial habenula nucleus. Doctoral thesis (Ph.D), UCL (University College London).

Text The_role_of_P2_receptors_in_fa.pdf Download (7MB)

Abstract

Fast excitatory glutamatergic and purinergic synaptic transmission was studied in acute slices of the rat medial habenula nucleus using whole-cell patch clamp recordings. The subunit composition of P2X receptors mediating fast purinergic transmission was investigated using the selective P2X1 and P2X2 antagonist NF279. This inhibited currents in a dose-dependent manner but the block was less than 100%. An additional facilitatory effect was evident at low concentrations. Glutamate transmission was modulated by the two P2Y receptor agonists UTP and UDP. Both low concentrations of UTP (10 and 30µM) and high concentrations of UDP (200µM) potentiated evoked glutamate currents. Analysis of failures revealed a presynaptic locus for both of these effects. Potentiation was long-lasting and inhibited by the P2 receptor antagonist RB2. Increasing the concentration of UTP inhibited evoked glutamate currents. This was also a presynaptic effect, as indicated by analysis of failures. Inhibition was reversible and not sensitive to RB2. α,β-methyleneATP, a desensitizing agonist at the P2X1 and P2X3 receptors and an antagonist at the P2X4 receptor, reversibly inhibited glutamate transmission in 50% of cells. Analysis of failures indicated a presynaptic effect. The non-selective P2 antagonist PPADS reversibly reduced the frequency of spontaneous miniature glutamatergic currents. The data indicates that glutamate afferents in the medial habenula posses at least two distinct presynaptic P2 receptors which facilitate release. A P2Y receptor mediates a novel form of long-term potentiation. A second P2 receptor (probably P2X) mediates brief facilitation.

Download activity - last month

Export as XMLCSVJSON

Download activity - last 12 months

Export as XMLCSVJSON

Downloads by country - last 12 months

Export as CSVXMLJSON

Archive Staff Only

View Item