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

Summary 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 α 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 α 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. Video Abstract Graphical Abstract Highlights • Ca V 2.1 dominate presynaptic active zones are not fully occupied by Ca V 2.1 channels • Presynaptic Ca V 2.1 channel numbers can increase regardless of developmental state • Higher synaptic vesicle release probability with increased Ca V 2.1 channel numbers • Ca V 2.1 completely competes away Ca V 2.2 channels, but not vice versa Lübbert et al. uncover that presynaptic active zones are not fully occupied by Ca V 2.1 during different states of neuronal circuit maturity. They propose that Ca V 2.1 levels in the presynaptic active zone can be increased to regulate neuronal circuit output. [ABSTRACT FROM AUTHOR]