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Updated: Jun 21, 2026

Microelectrode Array Recording of Sinoatrial Node Firing Rate to Identify Intrinsic Cardiac Pacemaking Defects in Mice
09:20

Microelectrode Array Recording of Sinoatrial Node Firing Rate to Identify Intrinsic Cardiac Pacemaking Defects in Mice

Published on: July 5, 2021

The cardiac pacemaker current

Mirko Baruscotti1, Andrea Barbuti, Annalisa Bucchi

  • 1Department of Biomolecular Sciences and Biotechnology, Laboratory of Molecular Physiology and Neurobiology, Università degli Studi di Milano, Centro Interuniversitario di Medicina Molecolare e Biofisica Applicata (CIMMBA), via Celoria 26, 20133 Milano, Italy. mirko.baruscotti@unimi.it

Journal of Molecular and Cellular Cardiology
|July 14, 2009
PubMed

Insights

The pacemaker current I(f), carried by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, primarily controls heart rate. HCN4 channels are crucial for sinoatrial node pacemaking and are targeted by heart rate-reducing drugs.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Electrophysiology

Background:

  • Cardiac rate in mammals is dictated by the diastolic depolarization duration in sinoatrial node (SAN) cells.
  • This depolarization is mainly governed by the pacemaker I(f) current, mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels (HCN1-4).
  • HCN4 is the predominant isoform in the SAN, and its role in pacemaking is evidenced by loss-of-function mutations causing cardiac rate disturbances.

Purpose of the Study:

  • To review recent findings on the contribution of f/HCN channels to cardiac pacemaking.
  • To highlight the significance of the I(f) current as a pharmacological target for heart rate modulation.
  • To discuss the role of HCN proteins in both physiological pacemaking and pathological conditions.

Main Methods:

  • Literature review focusing on recent research findings.
  • Analysis of the role of HCN channel isoforms in cardiac conduction system cells.
  • Examination of the pharmacological targeting of the I(f) current.

Main Results:

  • HCN4 is the most abundant HCN isoform in the SAN and is critical for normal heart rate.
  • Mutations in HCN genes can lead to cardiac rate disturbances.
  • The I(f) current is a validated target for drugs like ivabradine, used to reduce heart rate.
  • HCN channels are expressed at low levels in working myocytes but can be arrhythmogenic when overexpressed pathologically.

Conclusions:

  • HCN channels, particularly HCN4, are fundamental to cardiac pacemaking.
  • Dysregulation of HCN channel function can result in cardiac arrhythmias.
  • Targeting the I(f) current offers a therapeutic strategy for managing heart rate.

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