Abstract
Previously we found that the activation of P2Y receptors elicits a long-term enhancement of GABAergic transmission between cerebellar interneurons and Purkinje cells (PCs). We here employed peak-scaled non-stationary analysis (PS-NSFA) to further examine the mechanisms underlying the P2Y receptor-mediated enhancement of GABAergic synapses. Stimulation-evoked IPSCs (eIPSCs) were recorded from PCs in neonatal rat cerebellar slices. ATP (100μM) applied by perfusion increased the amplitude of eIPSCs to 132±4.4% of the control. Using PS-NSFA, the number and single channel conductance of GABAA receptors responsible for eIPSCs in PCs were determined. The single channel conductance increased significantly (159±10%, n=6) during the ATP-induced enhancement of eIPSCs, whereas there was no discernible change in the number of the receptors (93±6.3%). Furthermore, pretreatment with the protein kinase A inhibitor H-89, but not the calmodulin kinase II inhibitor KN-62, abolished the ATP-induced enhancement of eIPSCs. These results suggest that P2Y receptor activation enhances GABAergic transmission to cerebellar Purkinje cells through a long-term increase in the postsynaptic GABAA receptor conductance via cyclic AMP-protein kinase A-coupled signaling cascade. This is in accordance with the previous finding that a P2Y11 receptor subtype that stimulates the adenylyl cyclase-cyclic AMP-dependent pathway occurs in the mammalian cerebellum. [J Physiol Sci. 2007;57 Suppl:S230]
