Pacemaker channels and sinus node arrhythmia

Trends Cardiovasc Med. 2004 Jan;14(1):23-8. doi: 10.1016/j.tcm.2003.09.006.


Cardiac pacemaker activity is regulated by at least five different classes of ion channels and by the opposing influence of sympathetic and parasympathetic stimulation. Inactivation of several genes, including a subunit coding for the potassium channel activated by the muscarinic receptor, I(KACh); the calcium channel, I(Ca,); and the hyperpolarization-activated channel, I(f), results in sinus node arrhythmia. Inactivation of the gene for the hyperpolarization-activated, cyclic nucleotide-gated channel isoform HCN2 or HCN4 and the use of pacemaker channel blockers show that (a) HCN2 prevents the diastolic membrane potential from becoming too negative, (b) HCN4 is the major channel mediating sympathetic stimulation of the pacemaker activity, and (3) complete blockage of the I(f) current is compatible with slow sinus node rhythm.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Action Potentials*
  • Animals
  • Arrhythmia, Sinus / genetics
  • Arrhythmia, Sinus / physiopathology
  • Cyclic Nucleotide-Gated Cation Channels
  • Electrophysiology
  • Heart Rate / genetics*
  • Heart Rate / physiology
  • Humans
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ion Channels / drug effects
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Mice
  • Mice, Knockout
  • Muscle Proteins / genetics
  • Potassium Channels
  • Rabbits
  • Risk Factors
  • Sensitivity and Specificity
  • Sinoatrial Node / physiology*


  • Cyclic Nucleotide-Gated Cation Channels
  • HCN2 protein, human
  • Hcn2 protein, mouse
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ion Channels
  • Muscle Proteins
  • Potassium Channels