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The Journal of Neuroscience, December 3, 2003, 23(35):11229-11234

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Cellular/Molecular
Presynaptic Ryanodine-Sensitive Calcium Stores Contribute to Evoked Neurotransmitter Release at the Basket Cell-Purkinje Cell Synapse

Micaela Galante and Alain Marty

Laboratoire de Physiologie Cérébrale, Université Paris 5, 75006 Paris, France

Presynaptic terminals of cerebellar basket cells are known to contain ryanodine-sensitive calcium stores (RyCSs); recently, it has been shown that these stores control the frequency of miniature synaptic currents in the absence of presynaptic spiking. Here, using paired recordings of basket cell-Purkinje cell synapses, we show that blocking the RyCSs with high concentration of ryanodine decreases the mean amplitude of evoked IPSCs to 70% of the control value. The paired-pulse ratio and failure rate increase, indicating that the reduction stems from a decreased probability of evoked neurotransmitter release. Various control experiments eliminate the possibility of an indirect effect of ryanodine via activation of postsynaptic receptors. Prolonged application of cyclopiazonic acid, a blocker of the endoplasmic reticulum calcium pump, totally abolishes the ryanodine action. Our results indicate that calcium released from presynaptic RyCSs enhances the amplitude of evoked GABAergic synaptic currents. The precise mechanism by which calcium released from internal stores affect action potential-dependent release is unknown; however, our results suggest that these stores do not provide additional calcium for each presynaptic action potential; rather, they appear to enhance depolarization-induced calcium signals indirectly, perhaps by increasing the basal level of cytosolic calcium concentration in the vicinity of release sites.

Key words: basket cell; Purkinje cell; paired recordings; ryanodine; ryanodine-sensitive calcium stores; cerebellum; perforated-patch


Received July 29, 2003; revised October 16, 2003; accepted October 18, 2003.




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