Presynaptic Ca²⁺ buffers control the strength of a fast post-tetanic hyperpolarization mediated by the α3 Na⁺/K ⁺-ATPase

The excitability of CNS presynaptic terminals after a tetanic burst of action potentials is important for synaptic plasticity. The mechanisms that regulate excitability, however, are not well understood. Using direct recordings from the rat calyx of Held terminal, we found that a fast Na⁺/K ⁺-ATPase (NKA)-mediated post-tetanic hyperpolarization (PTH) controls the probability and precision of subsequent firing. Notably, increasing the concentration of internal Ca²⁺ buffers or decreasing Ca²⁺ influx led to larger PTH amplitudes, indicating that an increase in [Ca ²⁺](i) regulates PTH via inhibition of NKAs. The characterization for the first time of a presynaptic NKA pump current, combined with immunofluorescence staining, identified the α3-NKA isoform on calyx terminals. Accordingly, the increased ability of the calyx to faithfully fire during a high-frequency train as it matures is paralleled by a larger expression of α3-NKA during development. We propose that this newly discovered Ca²⁺ dependence 1of PTH is important in the post-burst excitability of nerve terminals.