Ca2.1 α Subunit Expression Regulates Presynaptic Ca2.1 Abundance and Synaptic Strength at a Central Synapse.

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