Calcium extrusion mechanisms in dendrites of mouse hippocampal CA1 inhibitory interneurons

• Published in: Cell calcium (Edinburgh) 2019-01, Vol.77, p.49-57
• Main Authors: Chamberland, Simon, Zamora Moratalla, Alfonsa, Topolnik, Lisa
• Format: Article
• Language: English
• Subjects: Action Potentials; Animals; CA1 Region, Hippocampal - cytology; CA1 Region, Hippocampal - metabolism; Calcium - metabolism; Calcium Signaling; Dendrites - metabolism; GABAergic interneuron; Inhibition; Interneurons - cytology; Interneurons - metabolism; Mice; Mitochondria calcium uniporter; Plasma membrane calcium ATPase; SERCA; Sodium-calcium exchanger; Synapses - metabolism
• ISSN: 0143-4160; 1532-1991
• DOI: 10.1016/j.ceca.2018.12.002

[Display omitted] •In dendrites of GABAergic interneurons, calcium removal is regulated by changes in activity.•Ca2+ clearance in interneuron dendrites is achieved through the Ca2+ ATPases, the Na+/Ca2+ exchanger, and the mitochondria Ca2+ uniporter.•The mitochondria Ca2+ uniporter is only activated at higher calcium loads produced by repetitive interneuron firing. 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 (Ca2+) mechanisms. To support this function, the spatiotemporal dynamics of dendritic Ca2+ elevations must be tightly regulated. While the dynamics of postsynaptic Ca2+ signaling through activation of different Ca2+ sources has been explored, the Ca2+ 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 Ca2+ imaging in acute mouse hippocampal slices, we characterized the Ca2+ extrusion mechanisms activated by Ca2+ transients (CaTs) associated with backpropagating action potentials (bAPs) in dendrites of hippocampal CA1 stratum radiatum interneurons. Our data showed that Ca2+ clearance increased as a function of activity, pointing to an activity-dependent recruitment of specific Ca2+ extrusion mechanisms. bAP-CaTs were significantly prolonged in the presence of the plasma membrane Ca2+ ATPase (PMCA) and Na+/Ca2+ exchanger (NCX) inhibitors as well as the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) and the mitochondria Ca2+ uniporter (MCU) blockers. While PMCA, NCX and SERCA pumps cooperated in the cytosolic Ca2+ removal at a wide range of concentrations, the MCU was only activated at higher Ca2+ loads produced by repetitive interneuron firing. These results identify a division of labor between distinct Ca2+ extrusion mechanisms shaping dendritic Ca2+ dynamics and possibly contributing to activity-dependent regulation of synaptic inputs in interneurons. In addition, the MCU activated by larger Ca2+ levels may be involved in the activity-dependent ATP production or interneuron-selective vulnerability associated with cytosolic Ca2+ overloads under pathological conditions.