Visualization of IP3 dynamics reveals a novel AMPA receptor-triggered IP3 production pathway mediated by voltage-dependent Ca2+ influx in Purkinje cells

IP3 signaling in Purkinje cells is involved in the regulation of cell functions including LTD. We have used a GFP-tagged pleckstrin homology domain to visualize IP3 dynamics in Purkinje cells. Surprisingly, IP3 production was observed in response not only to mGIuR activation, but also to AMPA receptor activation in Purkinje cells in culture. AMPA-induced IP3 production was mediated by depolarization-induced Call influx because it was mimicked by depolarization and was blocked by inhibition of the P-type Ca2+ channel. Furthermore, trains of complex spikes, elicited by climbing fiber stimulation (1 Hz), induced IP3 production in Purkinje cells in cerebellar slices. These results revealed a novel IP3 signaling pathway in Purkinje cells that can be elicited by synaptic inputs from climbing fibers.