Channelopathies linked to plasma membrane phosphoinositides.
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.
Logothetis
Diomedes E
DE
Department of Physiology and Biophysics, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, USA. delogothetis@vcu.edu
Petrou
Vasileios I
VI
Adney
Scott K
SK
Mahajan
Rahul
R
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000502:physiology; D053447:Channelopathies / Q000503:physiopathology*; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000502:physiology; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology; D050051:Transient Receptor Potential Channels / Q000502:physiology
D007473:Ion Channels; D019269:Phosphatidylinositol 4,5-Diphosphate; D024661:Potassium Channels, Inwardly Rectifying; D017470:Receptors, Glutamate; D018048:Receptors, Purinergic P2; D019837:Ryanodine Receptor Calcium Release Channel; D015222:Sodium Channels; D050051:Transient Receptor Potential Channels; D000252:Calcium-Transporting ATPases
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