Channelopathies linked to plasma membrane phosphoinositides

• Published in: Pflügers Archiv Vol. 460; no. 2; pp. 321 - 341
• Main Authors: Logothetis, Diomedes E., Petrou, Vasileios I., Adney, Scott K., Mahajan, Rahul
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-07-2010; Springer Nature B.V
• Subjects: Affinity; Animals; Biomedical and Life Sciences; Biomedicine; Calcium-Transporting ATPases - physiology; Cell Biology; Channelopathies - physiopathology; Channels; Diseases; Disorders; Human Physiology; Humans; Invited Review; Ion channels; Ion Channels - genetics; Ion Channels - physiology; Membranes; Molecular Medicine; Mutations; Neurosciences; Phosphatidylinositol 4,5-Diphosphate - physiology; Potassium Channels, Inwardly Rectifying - physiology; Proteins; Receptors; Receptors, Glutamate - physiology; Receptors, Purinergic P2 - physiology; Ryanodine Receptor Calcium Release Channel - physiology; Sodium Channels - physiology; Transient Receptor Potential Channels - physiology; Phosphoinositides; Channelopathies; Modulation of channel activity; Channel-PIP; Ion Channels; PIP; Channel activity; interactions
• ISSN: 0031-6768; 1432-2013
• DOI: 10.1007/s00424-010-0828-y

The plasma membrane phosphoinositide phosphatidylinositol 4,5-bisphosphate (PIP
2
) controls the activity of most ion channels tested thus far through direct electrostatic interactions. Mutations in channel proteins that change their apparent affinity to PIP
2
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 PIP
2
-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 PIP
2
promises to provide a mechanism by which defects on either the channel protein or the phosphoinositide levels can lead to disease.