Fast-spiking neurons in the brain, such as cortical intemeurons, cerebellar granule cells and auditory relay neurons, can fire at extraordinarily fast rates (up to 1 kHz) with minimal activity-dependent spike broadening, but the underlying mechanisms remain unknown.By directly recording presynaptic K+ currents from the calyx of Held synapse specialized in high-frequency auditory neurotransmission, we discovered that voltage-gated potassium currents from calyceal terminals evoked by both real and pseudo action potential trains facilitate in a frequency-dependent but Ca2+-independent manner in whole-cell mode or outside-out patches.Pair-pulse paradigms with varying inter-pulse intervals showed that this facilitation is inversely correlated with the inter-pulse interval, spike width and amplitude, and resides in both Dendrotoxin-sensitive low-threshold (Kv 1s) and TEA-sensitive high-threshold potassium channels (Kv3s).The robust facilitation can be recapitulated in CHO cells expressing Kvl.1/1.2 heteromeric or Kv3.1 homomeric channels.In both recombinant channels, we found that a brief depolarization shifts the voltage-dependence of potassium channels towards left and dramatically accelerates the activation and inactivation kinetics of K+ currents in response to the subsequent stimulus.These changes can be quantitatively described by a kinetic scheme model, in which there are two populations of channels (RESTING=R vs.