Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Pacemaker channels produce an instantaneous current.

Catherine Proenza1, Damiano Angoli, Eugene Agranovich

  • 1Ion Channel Laboratory, School of Kinesiology, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.

The Journal of Biological Chemistry
|December 14, 2001
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

An inter-subunit path is required for entropically-driven and negatively cooperative binding of cyclic nucleotides in the HCN2 channel.

Communications biology·2026
Same author

Electrophysiological Phenotyping of hiPSC-Derived Atrial Cardiomyocytes Using Automated Patch-Clamp: A Platform for Studying Atrial Inherited Arrhythmias.

Cells·2025
Same author

Selective amino acid formulation enhances anion secretion and restores function in cystic fibrosis mutations.

Frontiers in pharmacology·2025
Same author

Identifying sex similarities and differences in structure and function of the sinoatrial node in the mouse heart.

Frontiers in medicine·2024
Same author

Select amino acids recover cytokine-altered ENaC function in human bronchial epithelial cells.

PloS one·2024
Same author

LRMP inhibits cAMP potentiation of HCN4 channels by disrupting intramolecular signal transduction.

eLife·2024

The mouse HCN2 channel generates both a slow pacemaker current (I(h)) and a rapid instantaneous current (I(inst(HCN2))). These currents are modulated by intracellular factors and suggest multiple open states for HCN channels.

Area of Science:

  • Neuroscience
  • Cardiology
  • Molecular Biology

Background:

  • Spontaneous rhythmic activity in the heart and brain relies on pacemaker currents (I(h)).
  • These currents are generated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels.
  • The HCN2 isoform is a key player in generating these essential pacemaker currents.

Purpose of the Study:

  • To investigate the properties of the mouse HCN2 pacemaker channel.
  • To determine if HCN2 produces currents beyond the known slowly activating I(h).
  • To elucidate the mechanisms and characteristics of any additional currents generated by HCN2.

Main Methods:

  • Utilized electrophysiological recordings to measure currents in cells expressing HCN2 channels.
  • Investigated the effects of mutations (S306Q) and co-expression with accessory subunits (MiRP1) on channel activity.

Related Experiment Videos

  • Analyzed current properties including amplitude, reversal potentials, and sensitivity to intracellular ions (Cl-) and cAMP.

    • Main Results:

    • Identified a significant instantaneous current (I(inst(HCN2))) in addition to the canonical I(h) produced by HCN2.
    • Found I(inst(HCN2)) to be membrane-specific, correlated with I(h) amplitude, and modulated by intracellular Cl- and cAMP.
    • Demonstrated that a specific mutation (S306Q) affected I(h) but not I(inst(HCN2)), and that I(inst(HCN2)) was insensitive to Cs+ block.

    Conclusions:

    • HCN2 channels can generate both slowly activating I(h) and a distinct instantaneous current, I(inst(HCN2)).
    • These findings suggest HCN channels may contribute a background conductance in native tissues.
    • The data support the existence of at least two distinct open states for HCN channels.