Cardiotonic steroids (CTS), including the endogenous compound ouabain, modulate neuronal Na/K-ATPase (NKA) activity in a concentration-dependent manner, affecting neuronal survival and function. While high concentrations of ouabain are neurotoxic, endogenous levels of 0.1–1 nM exert neuroprotective effects and influence intracellular signaling. However, the effects of physiologically relevant ouabain concentrations on excitatory synaptic transmission remain unclear. In this study, we examined how 1 nM ouabain affects synaptic responses in rat hippocampal CA1 neurons. Using whole-cell patch-clamp recordings of evoked excitatory postsynaptic currents (EPSCs) and extracellular recordings of field excitatory postsynaptic potentials (fEPSPs), we found that ouabain enhances excitatory synaptic transmission, increasing EPSC amplitude and fEPSP slope by 35–50%. This effect was independent of NMDA receptor (NMDAR) activity. Ouabain reduced the magnitude of NMDAR-dependent long-term potentiation (LTP), but still augmented fEPSPs when applied after LTP induction. This implies separate additive mechanisms. These observations exhibit that ouabain, at concentrations corresponding to endogenous levels, facilitates basal excitatory synaptic transmission while partially suppressing LTP. We propose that ouabain exerts dual modulatory effects in hippocampal networks via distinct synaptic mechanisms.
Stepanenko et al. (Wed,) studied this question.