CaV2.1 α1 Subunit Expression Regulates Presynaptic CaV2.1 Abundance and Synaptic Strength at a Central Synapse

The abundance of presynaptic Ca(V)2 voltage-gated Ca2+ channels (Ca(V)2) at mammalian active zones (AZs) regulates the efficacy of synaptic transmission. It is proposed that presynaptic Ca(V)2 levels are saturated in AZs due to a finite number of slots that set Ca(V)2 subtype abundance and that Ca(V)2.1 cannot compete for Ca(V)2.2 slots. However, at most AZs, Ca(V)2.1 levels are highest and Ca(V)2.2 levels are developmentally reduced. To investigate Ca(V)2.1 saturation states and preference in AZs, we overexpressed the Ca(V)2.1 and Ca(V)2.2 alpha(1) subunits at the calyx of Held at immature and mature developmental stages. We found that AZs prefer Ca(V)2.1 to Ca(V)2.2. Remarkably, Ca(V)2.1 alpha(1) subunit overexpression drove increased Ca(V)2.1 currents and channel numbers and increased synaptic strength at both developmental stages examined. Therefore, we propose that Ca(V)2.1 levels in the AZ are not saturated and that synaptic strength can be modulated by increasing Ca(V)2.1 levels to regulate neuronal circuit output.