Sodium-potassium ATPase emerges as a player in hippocampal phenotypes of Angelman syndrome mice

Abstract

Angelman syndrome is a neurodevelopmental disorder characterized by intellectual disabilities, ataxia, and unusually happy affect. The hippocampal pyramidal cells of Angelman syndrome model mice have altered intrinsic membrane properties, which Kaphzan et al. (Cell Rep 4: 405-412, 2013) demonstrate can be corrected by genetic reduction of the α1-subunit of the sodium-potassium ATPase. Intriguingly, this manipulation also restores hippocampal long-term potentiation and learning. In this Neuro Forum, we discuss translational implications of this work and remaining questions left in its wake.

Keywords: Angelman syndrome; intrinsic excitability; long-term potentiation; sodium-potassium ATPase.

Fig. 1.

Na⁺/K⁺ exchange and signal transduction activity of the sodium-potassium ATPase. A: the sodium-potassium ATPase hydrolyzes ATP and translocates two potassium ions in and three sodium ions out of the cell. Ouabain and other cardiac glycosides like digoxin inhibit this activity. B: the α₁-subunit of the sodium-potassium ATPase associates with phospholipase C gamma (PLCγ) and the inositol triphosphate receptor (IP₃R). Ouabain binding stimulates α1-NaKA signal transduction activity to cause the release of calcium from the endoplasmic reticulum. DAG, diacylglycerol; PIP₂, phosphatidylinositol 4,5-bisphosphate.