Synaptically activated Ca2+ waves and NMDA spikes locally suppress voltage-dependent Ca2+ signalling in rat pyramidal cell dendrites

Abstract

Synaptically activated changes in dendritic [Ca2+]i affect many important physiological processes including synaptic plasticity and gene expression. The location, magnitude, and time course of these changes can determine which mechanisms are affected. Therefore, it is important to understand the processes that control and modulate these changes. One important source is Ca2+ entering through voltage gated Ca2+ channels opened by action potentials backpropagating over the dendrites (bAPs). Here we examine how [Ca2+]i changes, caused by regenerative Ca2+ release from internal stores (Ca2+ waves) or by regenerative Ca2+ entry through NMDA receptors (NMDA spikes) affect subsequent bAP evoked [Ca2+]i changes. These large [Ca2+]i increases suppressed the bAP signals in the regions where the preceding [Ca2+]i increases were largest. The suppression was proportional to the magnitude of the large [Ca2+]i change and was insensitive to kinase and phosphatase inhibitors, consistent with suppression due to Ca2+ dependent inhibition of Ca2+ channels.