Inhibition of presynaptic Na+/K+-ATPase reduces readily releasable pool size at the avian end-bulb of Held synapse

A glutamatergic end-bulb synapse in the avian nucleus magnocellularis relays temporal sound information from the auditory nerve. Here, we show that presynaptic Ne+/K+-ATPase (NKA) activity at this synapse contributes to the maintenance of the readily releasable pool (RRP) of vesicles, thereby preserving synaptic strength. Whole-cell voltage clamp recordings were made from chick brainstem slices to examine the effects of NKA blocker dihydroouabain (DHO) on synaptic transmission. DHO suppressed the amplitude of EPSCs in a dose-dependent manner. This suppression was caused by a decrease in the number of neurotransmitter quanta released because DHO increased the coefficient of variation of EPSC amplitude and reduced the frequency but not the amplitude of miniature EPSCs. Cumulative plots of EPSC amplitude during a stimulus train revealed that DHO reduced the RRP size without affecting vesicular release probability. DHO did not affect [Ca2+](i)-dependent processes, such as the paired-pulse ratio or recovery time course from the paired-pulse depression, suggesting a minimal effect on Ca2+ concentration in the presynaptic terminal. Using mathematical models of synaptic depression, we further demonstrated the contribution of RRP size to the synaptic strength during a high-frequency stimulus train to highlight the importance of presynaptic NKA in the auditory synapse. (C) 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.