Evidence map›Paper›PMID 37982354›Full record

ReviewProteins2025

The enigmatic HCN channels: A cellular neurophysiology perspective.

Poonam Mishra, Rishikesh Narayanan

Open access · hybridAbstract readReview
In one paragraph

Review in Proteins, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
4.9field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 33 citations in OpenAlex.

  1. Article
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  5. KArchiv der Pharmazie · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 2 institutions in 2 countries.

Poonam MishraDepartment of Neuroscience, Yale School of Medicine, Yale University, New Haven, Connecticut, USA.ORCID https://orcid.org/0000-0003-4174-4113
Rishikesh NarayananCellular Neurophysiology Laboratory, Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.ORCID https://orcid.org/0000-0002-1362-4635
Indian Institute of Science Bangalore · INYale University · US

Funding

Department of Biotechnology, Ministry of Science and Technology, IndiaHuman Frontier Science ProgramMinistry of EducationThe Wellcome Trust DBT India AllianceWellcome Trust
6 · The paper itself

Abstract

What physiological role does a slow hyperpolarization-activated ion channel with mixed cation selectivity play in the fast world of neuronal action potentials that are driven by depolarization? That puzzling question has piqued the curiosity of physiology enthusiasts about the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which are widely expressed across the body and especially in neurons. In this review, we emphasize the need to assess HCN channels from the perspective of how they respond to time-varying signals, while also accounting for their interactions with other co-expressing channels and receptors. First, we illustrate how the unique structural and functional characteristics of HCN channels allow them to mediate a slow negative feedback loop in the neurons that they express in. We present the several physiological implications of this negative feedback loop to neuronal response characteristics including neuronal gain, voltage sag and rebound, temporal summation, membrane potential resonance, inductive phase lead, spike triggered average, and coincidence detection. Next, we argue that the overall impact of HCN channels on neuronal physiology critically relies on their interactions with other co-expressing channels and receptors. Interactions with other channels allow HCN channels to mediate intrinsic oscillations, earning them the "pacemaker channel" moniker, and to regulate spike frequency adaptation, plateau potentials, neurotransmitter release from presynaptic terminals, and spike initiation at the axonal initial segment. We also explore the impact of spatially non-homogeneous subcellular distributions of HCN channels in different neuronal subtypes and their interactions with other channels and receptors. Finally, we discuss how plasticity in HCN channels is widely prevalent and can mediate different encoding, homeostatic, and neuroprotective functions in a neuron. In summary, we argue that HCN channels form an important class of channels that mediate a diversity of neuronal functions owing to their unique gating kinetics that made them a puzzle in the first place.

Indexed as

Action PotentialsHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsNeuronsAnimalsHumansIon Channel GatingHyperpolarization-Activated Cyclic Nucleotide-Gated Channelshomeostasisimpedanceinductanceintrinsic excitabilityintrinsic plasticityoscillationsresonancetemporal summation

Identifiers

PMID37982354
PMCPMC7616572
OpenAlexW4388831410

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.