Contributions of SERCA pump and ryanodine-sensitive stores to presynaptic residual Ca2+

The presynaptic Ca2+ signal, which triggers vesicle release, disperses to a broadly distributed residual [Ca2+] ([Ca2+](res)) that plays an important role in synaptic plasticity. We have previously reported a slowing in the decay timecourse of [Ca2+](res) during the second of paired pulses. In this study, we investigated the contributions of organelle and plasma membrane Ca2+ flux pathways to the reduction of effectiveness of [Ca2+](res) clearance during short-term plasticity in Schaffer collateral terminals in the CA1 field of the hippocampus. We show that the slowed decay timecourse is mainly the result of a transport-dependent Ca2+ clearance process; that presynaptic caffeine-sensitive Ca2+ stores are not functionally loaded in the unstimulated terminal, but that these stores can effectively take up Ca2+ even during high frequency trains of stimuli; and that a rate limiting step of sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) kinetics following the first pulse is responsible for a large portion of the observed slowing of [Ca2+](res) clearance during the second pulse. We were able to accurately fit our [Ca2+](res) data with a kinetic model based on these observations and this model predicted a reduction in availability of unbound SERCA during paired pulses, but no saturation of Ca2+ buffer in the endoplasmic reticulum. (C) 2010 Elsevier Ltd. All rights reserved.