An axon-specific expression of HCN channels catalyzes fast action potential signaling in GABAergic interneurons

Nat Commun. 2020 May 7;11(1):2248. doi: 10.1038/s41467-020-15791-y.

Abstract

During high-frequency network activities, fast-spiking, parvalbumin-expressing basket cells (PV+-BCs) generate barrages of fast synaptic inhibition to control the probability and precise timing of action potential (AP) initiation in principal neurons. Here we describe a subcellular specialization that contributes to the high speed of synaptic inhibition mediated by PV+-BCs. Mapping of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel distribution in rat hippocampal PV+-BCs with subcellular patch-clamp methods revealed that functional HCN channels are exclusively expressed in axons and completely absent from somata and dendrites. HCN channels not only enhance AP initiation during sustained high-frequency firing but also speed up the propagation of AP trains in PV+-BC axons by dynamically opposing the hyperpolarization produced by Na+-K+ ATPases. Since axonal AP signaling determines the timing of synaptic communication, the axon-specific expression of HCN channels represents a specialization for PV+-BCs to operate at high speed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Axons
  • Dendrites / metabolism
  • GABAergic Neurons / metabolism*
  • Interneurons / metabolism*
  • Male
  • Rats
  • Rats, Wistar
  • Signal Transduction / physiology
  • Sodium-Potassium-Exchanging ATPase / metabolism

Substances

  • Sodium-Potassium-Exchanging ATPase