Calcium extrusion mechanisms in dendrites of mouse hippocampal CA1 inhibitory interneurons.

TitleCalcium extrusion mechanisms in dendrites of mouse hippocampal CA1 inhibitory interneurons.
Publication TypeJournal Article
Year of Publication2019
AuthorsChamberland, S, Moratalla, AZamora, Topolnik, L
JournalCell Calcium
Volume77
Pagination49-57
Date Published2019 Jan
ISSN1532-1991
Abstract

Local circuit GABAergic inhibitory interneurons control the integration and transfer of information in many brain regions. Several different forms of plasticity reported at interneuron excitatory synapses are triggered by cell- and synapse-specific postsynaptic calcium (Ca) mechanisms. To support this function, the spatiotemporal dynamics of dendritic Ca elevations must be tightly regulated. While the dynamics of postsynaptic Ca signaling through activation of different Ca sources has been explored, the Ca extrusion mechanisms that operate in interneuron dendrites during different patterns of activity remain largely unknown. Using a combination of whole-cell patch-clamp recordings and two-photon Ca imaging in acute mouse hippocampal slices, we characterized the Ca extrusion mechanisms activated by Ca transients (CaTs) associated with backpropagating action potentials (bAPs) in dendrites of hippocampal CA1 stratum radiatum interneurons. Our data showed that Ca clearance increased as a function of activity, pointing to an activity-dependent recruitment of specific Ca extrusion mechanisms. bAP-CaTs were significantly prolonged in the presence of the plasma membrane Ca ATPase (PMCA) and Na/Ca exchanger (NCX) inhibitors as well as the sarco/endoplasmic reticulum Ca ATPase (SERCA) and the mitochondria Ca uniporter (MCU) blockers. While PMCA, NCX and SERCA pumps cooperated in the cytosolic Ca removal at a wide range of concentrations, the MCU was only activated at higher Ca loads produced by repetitive interneuron firing. These results identify a division of labor between distinct Ca extrusion mechanisms shaping dendritic Ca dynamics and possibly contributing to activity-dependent regulation of synaptic inputs in interneurons. In addition, the MCU activated by larger Ca levels may be involved in the activity-dependent ATP production or interneuron-selective vulnerability associated with cytosolic Ca overloads under pathological conditions.

DOI10.1016/j.ceca.2018.12.002
Alternate JournalCell Calcium
PubMed ID30530093