Characterisation of P2 receptors in mouse superior cervical ganglia
P2 receptors are activated by nucleotides, and are subdivided into two groups: P2X receptors (ligand gated ion channels) and P2Y receptors (GPCR's), of which there are seven and eight isoforms respectively. These receptors have a widespread distribution, and are abundant in neuronal tissue. The aim of this thesis was to characterise the P2 receptors expressed in mouse superior cervical ganglia (SCG). A combination of whole-cell patch clamp and fluorescent Ca2+ imaging was used to demonstrate that ~ 80% of neurons expressed a receptor with the characteristics of the P2X2 subunit. In addition, ~ 9% of these neurons were also found to respond to the selective agonist a,b-meATP. Cells from P2X1 knockout mice were not sensitive to a,b-meATP, implying that this subunit was functionally expressed in SCG neurons. Furthermore, the a,b-meATP response had the ionic modulation properties of the P2X2 receptor, indicating the presence of a P2X1/2 heteromer. Fluorescent Ca2+ imaging showed that there were three isoforms of Gq coupled P2Y receptor in mouse SCG neurons. Neurons from P2Y1 knockout mice were used to confirm the expression of P2Y1 receptors. UDP activated a small population of neurons, and this was probably due to expression of P2Y6 receptors. A UTP sensitive receptor was also present but its identity could not be determined due to a novel profile of responses. SCG glial cells expressed the same receptors as neurons, with the exception that the UTP sensitive subunit was probably a P2Y2 receptor in glia. This thesis has demonstrated that there is heterogeneous expression of P2 receptors in mouse SCG neurons and glia, and that individual cells can express multiple isoforms. This could indicate the use of chemical coding of neurotransmission dependent on the target tissue, and could have implications for intercellular communication between neurons and glia.