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

Abstract

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 Ca(2+) buffers or decreasing Ca(2+) 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 alpha3-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 alpha3-NKA during development. We propose that this newly discovered Ca(2+) dependence of PTH is important in the post-burst excitability of nerve terminals.

Na, K-ATPase α3 is a death target of Alzheimer patient amyloid-β assembly

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Na,K-ATPase signal transduction triggers CREB activation and dendritic growth

“…S2). Furthermore, in the brain, there are multiple Na,K-ATPase isoforms that each have cell-type-specific and developmentalspecific expression patterns (33,42) as well as different ouabain affinities (31,42). These spatial and temporal expression patterns of Na,K-ATPase isoform remain largely unknown but may be involved in the development and wiring of the brain.…”

“…1A and 1B). The effect of ouabain on Na,K-ATPase varies in a dose-dependent manner (31,32); therefore, cortical neurons were exposed to graded concentrations of ouabain, and dendritic arbor growth was examined. As shown in Fig.…”

“…Previous studies have shown that Na,K-ATPase isoforms have different affinities for ouabain (31) as well as cell-type-specific and developmental-specific expression patterns (33). The ␣3-and ␣2-isoforms of Na,K-ATPase have a higher affinity to ouabain as compared with the rather insensitive ␣1-isoform (31,32). Thus, we determined the identity of the ␣-subunit isoforms expressed in rat cortical neurons in primary culture by reverse transcription-polymerase chain reaction (RT-PCR) using sequence-specific primers.…”