Neurons convey information in bursts of spikes across chemical synapses where the fidelity of information transfer critically depends on synaptic input-output relationship. With a limited number of synaptic vesicles (SVs) in the readily releasable pool (RRP), how nerve terminals sustain transmitter release during intense activity remains poorly understood. Here we report that presynaptic K + currents evoked by spikes facilitate in a Ca 2+ -independent but frequency- and voltage-dependent manner. Experimental evidence and computer simulations demonstrate that this facilitation originates from dynamic transition of intermediate gating states of voltage-gated K + channels (Kvs), and specifically attenuates spike amplitude and inter-spike potential during high-frequency firing. Single or paired recordings from a mammalian central synapse further reveal that facilitation of Kvs constrains presynaptic Ca 2+ influx, thereby efficiently allocating SVs in the RRP to drive postsynaptic spiking at high rates. We conclude that presynaptic Kv facilitation imparts neurons with a powerful control of transmitter release to dynamically support high-fidelity neurotransmission.
Bibliographical noteFunding Information:
This work was supported by individual Operating Grants from the Canadian Institutes of Health Research and Canada Research Chair (to L.-Y.W.); China-Canada Joint Health Research Initiative Grant (to L.-Y.W. and Z.Z.); The National Basic Research Program of China (2010CB529804) and the National Science Foundation of China (30971179 and 31170814; to J.D.). We thank Drs Michael W. Salter, Steve Prescott and Milton Charlton for their critical inputs to a previous version of this manuscript, Stéphanie Ratté for her technical support with dynamic clamp, Lu Han for transfecting and maintaining CHO cell lines, and other members of the Wang Laboratory for their assistance and discussions.