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Pflugers Arch. 2007 Oct;455(1):105-13. Epub 2007 Jul 11.

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

Author information

1
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore.

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 (I (Kr)) 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 I (Kr) 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.

PMID:
17622552
DOI:
10.1007/s00424-007-0292-5
[Indexed for MEDLINE]

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