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Pacemaker current and automatic rhythms: toward a molecular understanding.

I S Cohen1, R B Robinson

  • 1Department of Physiology and Biophysics, Stony Brook University, Room 150 Basic Science Tower, Stony Brook, NY 11794-8661, USA.

Handbook of Experimental Pharmacology
|April 14, 2006
PubMed
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The pacemaker current (If), generated by HCN channels, is a promising target for treating heart rhythm disorders. Its unique diastolic function allows for selective modulation of cardiac pacemakers without affecting repolarization.

Area of Science:

  • Cardiac Electrophysiology
  • Molecular Cardiology
  • Pharmacology

Background:

  • The sinoatrial node and His-Purkinje system are key cardiac pacemakers.
  • Understanding their ionic basis is crucial for treating rhythm disorders.

Purpose of the Study:

  • To discuss the ionic basis of cardiac automaticity.
  • To identify potential therapeutic targets for rhythm disorders.
  • To review the pacemaker current (If) as an ideal target.

Main Methods:

  • Review of biophysical and molecular characteristics of the If current.
  • Examination of HCN gene family's role.
  • Assessment of pharmacologic and genetic therapy approaches.

Main Results:

Related Experiment Videos

  • The If current, generated by HCN channels, exhibits diastolic function and regional differences.
  • These characteristics make it an ideal target for selective pacemaker modulation.
  • Progress in developing selective If-targeting agents and gene therapies is reviewed.

Conclusions:

  • The If current is a prime target for pharmacologic and genetic therapies of cardiac rhythm disorders.
  • Selective targeting can modulate primary and secondary pacemakers without affecting action potential repolarization.