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The funny current in genetically modified mice.

Mattia L DiFrancesco1, Pietro Mesirca2, Isabelle Bidaud2

  • 1Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, Montpellier, France; LabEx Ion Channels Science and Therapeutics (ICST), France.

Progress in Biophysics and Molecular Biology
|June 15, 2021
PubMed
Summary
This summary is machine-generated.

The funny current (If) is crucial for heart rate regulation. Genetically modified mice have significantly advanced our understanding of If

Keywords:
Cardiac pacemaker activityConduction systemFunny currentGenetically modified miceRhythmogenesisSinoatrial node

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Area of Science:

  • Cardiology
  • Molecular Physiology
  • Cardiac Electrophysiology

Background:

  • The hyperpolarization-activated funny current (If) has been studied since 1979 for its role in cardiac pacemaker activity.
  • The rabbit was the primary model for If research for over two decades.
  • Mouse models, particularly genetically modified ones, have become essential for studying cardiac pacemaker mechanisms.

Purpose of the Study:

  • To review the influence of mouse genetics on current knowledge of the funny current's role in cardiac pacemaker physiology and pathophysiology.
  • To highlight insights gained from genetically modified mice regarding If's role in intrinsic automaticity and conduction system myocytes.
  • To discuss the contribution of gene targeting of HCN channel isoforms to understanding If's role in parasympathetic heart rate regulation.

Main Methods:

  • Review of existing literature on the funny current (If) and cardiac pacemaker activity.
  • Focus on studies utilizing genetically modified mouse models.
  • Integration of findings from in-vivo exploration techniques, imaging, genetics, and genomics.

Main Results:

  • Genetically modified mice have provided critical insights into the in-vivo role of If in automaticity and conduction system function.
  • Gene targeting of HCN channel isoforms has elucidated If's involvement in parasympathetic nervous system regulation of heart rate.
  • Advancements in genetic and physiological techniques have deepened the understanding of If's mechanisms.

Conclusions:

  • Genetically modified mouse models are invaluable for dissecting the complex roles of the funny current (If) in cardiac function.
  • Understanding If's genetic underpinnings is key to comprehending heart rate regulation by the autonomic nervous system.
  • This review synthesizes recent advancements, emphasizing the impact of mouse genetics on If research.