1. Ca V 2.1 α 1 Subunit Expression Regulates Presynaptic Ca V 2.1 Abundance and Synaptic Strength at a Central Synapse.
- Author
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Lübbert M, Goral RO, Keine C, Thomas C, Guerrero-Given D, Putzke T, Satterfield R, Kamasawa N, and Young SM Jr
- Subjects
- Animals, Animals, Newborn, Biophysics, Cadmium Chloride pharmacology, Calcium metabolism, Calcium Channel Blockers pharmacology, Calcium Channels, N-Type genetics, Electric Stimulation, Female, Green Fluorescent Proteins genetics, Green Fluorescent Proteins metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neurotransmitter Agents metabolism, Presynaptic Terminals ultrastructure, Synapses ultrastructure, Brain Stem cytology, Calcium Channels, N-Type metabolism, Presynaptic Terminals physiology, Synapses physiology, Synaptic Transmission genetics
- Abstract
The abundance of presynaptic Ca
V 2 voltage-gated Ca2+ channels (CaV 2) at mammalian active zones (AZs) regulates the efficacy of synaptic transmission. It is proposed that presynaptic CaV 2 levels are saturated in AZs due to a finite number of slots that set CaV 2 subtype abundance and that CaV 2.1 cannot compete for CaV 2.2 slots. However, at most AZs, CaV 2.1 levels are highest and CaV 2.2 levels are developmentally reduced. To investigate CaV 2.1 saturation states and preference in AZs, we overexpressed the CaV 2.1 and CaV 2.2 α1 subunits at the calyx of Held at immature and mature developmental stages. We found that AZs prefer CaV 2.1 to CaV 2.2. Remarkably, CaV 2.1 α1 subunit overexpression drove increased CaV 2.1 currents and channel numbers and increased synaptic strength at both developmental stages examined. Therefore, we propose that CaV 2.1 levels in the AZ are not saturated and that synaptic strength can be modulated by increasing CaV 2.1 levels to regulate neuronal circuit output. VIDEO ABSTRACT., (Copyright © 2018 Elsevier Inc. All rights reserved.)- Published
- 2019
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