HCN Channels and Heart Rate

Molecules. 2012 Apr 5;17(4):4225-35. doi: 10.3390/molecules17044225.

Abstract

Hyperpolarization and Cyclic Nucleotide (HCN) -gated channels represent the molecular correlates of the "funny" pacemaker current (I(f)), a current activated by hyperpolarization and considered able to influence the sinus node function in generating cardiac impulses. HCN channels are a family of six transmembrane domain, single pore-loop, hyperpolarization activated, non-selective cation channels. This channel family comprises four members: HCN1-4, but there is a general agreement to consider HCN4 as the main isoform able to control heart rate. This review aims to summarize advanced insights into the structure, function and cellular regulation of HCN channels in order to better understand the role of such channels in regulating heart rate and heart function in normal and pathological conditions. Therefore, we evaluated the possible therapeutic application of the selective HCN channels blockers in heart rate control.

Publication types

  • Review

MeSH terms

  • Animals
  • Arrhythmias, Cardiac / drug therapy
  • Arrhythmias, Cardiac / genetics
  • Biological Clocks / drug effects
  • Biological Clocks / physiology
  • Cardiovascular Agents / pharmacology
  • Cardiovascular Agents / therapeutic use
  • Circadian Rhythm / drug effects
  • Circadian Rhythm / physiology
  • Cyclic Nucleotide-Gated Cation Channels / drug effects
  • Cyclic Nucleotide-Gated Cation Channels / genetics
  • Cyclic Nucleotide-Gated Cation Channels / metabolism*
  • Disease Models, Animal
  • Heart Rate / drug effects
  • Heart Rate / physiology*
  • Humans
  • Membrane Transport Modulators / pharmacology
  • Membrane Transport Modulators / therapeutic use
  • Mice
  • Mice, Knockout
  • Mutation
  • Sinoatrial Node / drug effects
  • Sinoatrial Node / physiology

Substances

  • Cardiovascular Agents
  • Cyclic Nucleotide-Gated Cation Channels
  • Membrane Transport Modulators