Phosphatidylinositol 4,5-bisphosphate interactions with the HERG K + channel

Jin Song Bian, Thomas V. McDonald

Research output: Contribution to journalReview article

33 Scopus citations

Abstract

Regulation of ion channel activity plays a central role in controlling heart rate, rhythm, and contractility responses to cardiovascular demands. Dynamic beat-to-beat regulation of ion channels is precisely adjusted by autonomic stimulation of cardiac G protein-coupled receptors. The rapidly activating delayed rectifier K+ current (IKr) is produced by the channel that is encoded by human ether-a-gogo-related gene (HERG) and is essential for the proper repolarization of the cardiac myocyte at the end of each action potential. Reduction of IKr via HERG mutations or drug block can lead to lethal cardiac tachyarrhythmias. Autonomic regulation of HERG channels is an area of active investigation with the emerging picture of a complex interplay of signal transduction events, including kinases, second messengers, and protein-protein interactions. A recently described pathway for regulation of HERG is through channel interaction with the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2). Changes in cellular PIP2 concentrations may occur with Gq-coupled receptor activation. Here, we review the evidence for PIP2-HERG interactions, its potential biological significance, and unfilled gaps in our understanding of this regulatory mechanism.

Original languageEnglish (US)
Pages (from-to)105-113
Number of pages9
JournalPflugers Archiv European Journal of Physiology
Volume455
Issue number1
DOIs
Publication statusPublished - Oct 1 2007

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Keywords

  • Adrenergic
  • Cardiac potassium current
  • EAG family
  • Phospholipid
  • Potassium channel
  • Topical review

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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