Tachycardia-bradycardia syndrome: Electrophysiological mechanisms and future therapeutic approaches (Review)

Int J Mol Med. 2017 Mar;39(3):519-526. doi: 10.3892/ijmm.2017.2877. Epub 2017 Feb 6.


Sick sinus syndrome (SSS) encompasses a group of disorders whereby the heart is unable to perform its pacemaker function, due to genetic and acquired causes. Tachycardia‑bradycardia syndrome (TBS) is a complication of SSS characterized by alternating tachycardia and bradycardia. Techniques such as genetic screening and molecular diagnostics together with the use of pre-clinical models have elucidated the electrophysiological mechanisms of this condition. Dysfunction of ion channels responsible for initiation or conduction of cardiac action potentials may underlie both bradycardia and tachycardia; bradycardia can also increase the risk of tachycardia, and vice versa. The mainstay treatment option for SSS is pacemaker implantation, an effective approach, but has disadvantages such as infection, limited battery life, dislodgement of leads and catheters to be permanently implanted in situ. Alternatives to electronic pacemakers are gene‑based bio‑artificial sinoatrial node and cell‑based bio‑artificial pacemakers, which are promising techniques whose long-term safety and efficacy need to be established. The aim of this article is to review the different ion channels involved in TBS, examine the three‑way relationship between ion channel dysfunction, tachycardia and bradycardia in TBS and to consider its current and future therapies.

Publication types

  • Review

MeSH terms

  • Animals
  • Bradycardia / etiology*
  • Bradycardia / metabolism*
  • Bradycardia / physiopathology
  • Bradycardia / therapy
  • Calcium / metabolism
  • Electrophysiological Phenomena
  • Gap Junctions / metabolism
  • Humans
  • Ion Channels / metabolism
  • Sick Sinus Syndrome / complications
  • Sinoatrial Node / metabolism
  • Sinoatrial Node / physiopathology
  • Syndrome
  • Tachycardia / etiology*
  • Tachycardia / metabolism*
  • Tachycardia / physiopathology
  • Tachycardia / therapy


  • Ion Channels
  • Calcium