Evidence that protons act as neurotransmitters at vestibular hair cell–calyx afferent synapses

Present data support the conclusion that protons serve as an important neurotransmitter to convey excitatory stimuli from inner ear type I vestibular hair cells to postsynaptic calyx nerve terminals. Time-resolved pH imaging revealed stimulus-evoked extrusion of protons from hair cells and a subsequent buildup of [ H ⁺] within the confined chalice-shaped synaptic cleft (ΔpH ∼ −0.2). Whole-cell voltage-clamp recordings revealed a concomitant nonquantal excitatory postsynaptic current in the calyx terminal that was causally modulated by cleft acidification. The time course of [ H ⁺] buildup limits the speed of this intercellular signaling mechanism, but for tonic signals such as gravity, protonergic transmission offers a significant metabolic advantage over quantal excitatory postsynaptic currents—an advantage that may have driven the proliferation of postsynaptic calyx terminals in the inner ear vestibular organs of contemporary amniotes.