DISTRIBUTION PROFILE AND RATIO OF CAV2 CHANNELS AND THE PLASMA MEMBRANE CA2+-ATPASE IN CENTRAL NEURONS
01/29/2020
Botond Gaál1, 2, Ákos Kulik2, 3
1 Department of Anatomy, Histology and Embryology, Faculty of Medicine, University of Debrecen, Hungary
2 Institute of Physiology II, Faculty of Medicine, University of Freiburg, Freiburg, Germany
3 Center for Biological Signaling Studies (BIOSS), University of Freiburg, Freiburg, Germany
In central neurons, calcium (Ca2+) signaling controls a variety of fundamental processes and reaction pathways, including neurotransmitter release. These processes are switched on by influx of Ca2+ into the cytosol of dendritic and axonal compartments of neurons, partially through voltage-activated Ca2+ channels (Cav), and they are switched off by the concerted action of various Ca2+ transporters that extrude Ca2+ ions from the cytoplasm. In neurons, one of the most abundant proteins responsible for Ca2+ clearance is the plasma membrane Ca2+-ATPase (PMCA), which transports Ca2+ to the extracellular space. Here, we combined the high-resolution freeze-fracture replica labeling immunoelectron microscopy with quantitative analyzed immunoreactivity for Cav2.1 (P/Q-type) channel, Cav2.2 (N-type) channel, and PMCA to determine the distribution pattern, density, and ratio of Cavs and transporter in cerebellar Purkinje cell dendrites and parallel fiber varicosities, as well as in dendritic shafts of hippocampal CA1 pyramidal cells and in Schaffer collaterals. The ratio of PMCA to Cav2 channels was 40:1 and 10:1 in dendritic shafts of Purkinje cells and CA1 pyramidal cells, respectively. Whereas in axon terminals of cerebellar granule cells and Schaffer collaterals the intensity of immunoreactivity for Cav2 channels was 5-fold and 30-fold higher than that of PMCA, respectively. Together, these results provide morphological evidence of (i) the predominant presynaptic localization of both Cav2.1 and Cav2.2 channels, (ii) the differential surface density of PMCAs in pre- and postsynaptic compartments, suggesting a preferential role of PMCAs in regulation of dendritic Ca2+ signaling. Fund:Deutsche Forschungsgemeinschaft FOR 2134 TP4, OTKA K 115471