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

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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… Click to show full 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. The precise subcellular location of ion channels is a key determinant of their functions. Here, subcellular patch-clamp recordings demonstrate that an axon-specific expression of HCN channels facilitates the initiation and propagation of action potentials in parvalbumin-expressing basket cells.

Keywords: expression hcn; specific expression; hcn; hcn channels; axon specific; action

Journal Title: Nature Communications
Year Published: 2020

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