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Channelopathies linked to plasma membrane phosphoinositides

  • Invited Review
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Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

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-PIP2 interactions ought to be tested. Similarly, diseases that are linked to disorders of the phosphoinositide pathway result in altered PIP2 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.

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Acknowledgments

We would like to thank past and present members of the Logothetis lab, whose dedicated efforts in studying phosphoinositide control of ion channel activity have culminated to the insights presented in this review. This work was supported by NIH grants HL059949 and HL090882 to DEL. RM was supported by an NIH NHLBI F30 pre-doctoral grant award.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, Virginia Commonwealth University, School of Medicine, Richmond, VA, 23298, USA

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

  2. Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, 10029, USA

    Vasileios I. Petrou

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  1. Diomedes E. Logothetis
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  2. Vasileios I. Petrou
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  3. Scott K. Adney
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Correspondence to Diomedes E. Logothetis.

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Logothetis, D.E., Petrou, V.I., Adney, S.K. et al. Channelopathies linked to plasma membrane phosphoinositides. Pflugers Arch - Eur J Physiol 460, 321–341 (2010). https://doi.org/10.1007/s00424-010-0828-y

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  • DOI: https://doi.org/10.1007/s00424-010-0828-y

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