A BK channel-mediated feedback pathway links single-synapse activity with action potential sharpening in repetitive firing

Sci Adv. 2018 Jul 4;4(7):eaat1357. doi: 10.1126/sciadv.aat1357. eCollection 2018 Jul.


Action potential shape is a major determinant of synaptic transmission, and mechanisms of spike tuning are therefore of key functional significance. We demonstrate that synaptic activity itself modulates future spikes in the same neuron via a rapid feedback pathway. Using Ca2+ imaging and targeted uncaging approaches in layer 5 neocortical pyramidal neurons, we show that the single spike-evoked Ca2+ rise occurring in one proximal bouton or first node of Ranvier drives a significant sharpening of subsequent action potentials recorded at the soma. This form of intrinsic modulation, mediated by the activation of large-conductance Ca2+/voltage-dependent K+ channels (BK channels), acts to maintain high-frequency firing and limit runaway spike broadening during repetitive firing, preventing an otherwise significant escalation of synaptic transmission. Our findings identify a novel short-term presynaptic plasticity mechanism that uses the activity history of a bouton or adjacent axonal site to dynamically tune ongoing signaling properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Calcium / metabolism
  • Evoked Potentials / drug effects
  • Female
  • Large-Conductance Calcium-Activated Potassium Channels / antagonists & inhibitors
  • Large-Conductance Calcium-Activated Potassium Channels / metabolism*
  • Male
  • Neurons / drug effects
  • Neurons / physiology
  • Patch-Clamp Techniques
  • Peptides / pharmacology
  • Potassium Channel Blockers / pharmacology
  • Rats
  • Rats, Wistar
  • Synapses / metabolism*


  • Large-Conductance Calcium-Activated Potassium Channels
  • Peptides
  • Potassium Channel Blockers
  • iberiotoxin
  • Calcium