Channelopathies linked to plasma membrane phosphoinositides

Diomedes E. Logothetis, Vasileios I. Petrou, Scott K. Adney, Rahul Mahajan

Research output: Contribution to journalReview articlepeer-review

83 Scopus citations

Abstract

The plasma membrane phosphoinositide phosphatidylinositol 4,5-bisphosphate (PIP2) controls the activity of most ion channels tested thus far through direct electrostatic interactions. Mutations in channel proteins that change their apparent affinity to PIP2 can lead to channelopathies. Given the fundamental role that membrane phosphoinositides play in regulating channel activity, it is surprising that only a small number of channelopathies have been linked to phosphoinositides. This review proposes that for channels whose activity is PIP2-dependent and for which mutations can lead to channelopathies, the possibility that the mutations alter channel-PIP 2 interactions ought to be tested. Similarly, diseases that are linked to disorders of the phosphoinositide pathway result in altered PIP 2 levels. In such cases, it is proposed that the possibility for a concomitant dysregulation of channel activity also ought to be tested. The ever-growing list of ion channels whose activity depends on interactions with PIP2 promises to provide a mechanism by which defects on either the channel protein or the phosphoinositide levels can lead to disease.

Original languageEnglish (US)
Pages (from-to)321-341
Number of pages21
JournalPflugers Archiv European Journal of Physiology
Volume460
Issue number2
DOIs
StatePublished - Jul 2010
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

Keywords

  • Channel activity
  • Channel-PIP interactions
  • Channelopathies
  • Ion channels
  • Modulation of channel activity
  • PIP
  • Phosphoinositides

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