The Na,K-ATPase α2 Isoform Is Expressed in Neurons, and Its Absence Disrupts Neuronal Activity in Newborn Mice

Abstract

Na,K-ATPase is an ion transporter that impacts neural and glial physiology by direct electrogenic activity and the modulation of ion gradients. Its three isoforms in brain have cell-type and development-specific expression patterns. Interestingly, our studies demonstrate that in late gestation, the ␣2 isoform is widely expressed in neurons, unlike in the adult brain, in which ␣2 has been shown to be expressed primarily in astrocytes. This unexpected distribution of ␣2 isoform expression in neurons is interesting in light of our examination of mice lacking the ␣2 isoform which fail to survive after birth. These animals showed no movement; however, defects in gross brain development, muscle contractility, neuromuscular transmission, and lung development were ruled out. Akinesia suggests a primary neuronal defect and electrophysiological recordings in the pre-Bö tzinger complex, the brainstem breathing center, showed reduction of respiratory rhythm activity, with less regular and smaller population bursts. These data demonstrate that the Na,K-ATPase ␣2 isoform could be important in the modulation of neuronal activity in the neonate.

First case of compound heterozygosity in Na,K-ATPase gene ATP1A2 in familial hemiplegic migraine

“…In knock-out Atp1a2 mice, however, homozygosity of two totally non-functional alleles is incompatible with life as pups die immediately after birth because they are unable to start breathing due to altered neuronal activity in respiratory neurons. 13 The presence of two ATP1A2 mutations in the proband causes a more severe phenotype compared to the milder FHM phenotype of her aunt, who carries only the I286T mutation. Hemiplegic migraine in the proband occurs at a lower age of onset, with a higher frequency and a longer duration of attacks that are always associated with hemiplegia.…”

Plasma Membrane-Cytoskeleton-Endoplasmic Reticulum Complexes in Neurons and Astrocytes

“…The Na ϩ pump ␣1 isoform is expressed in virtually all cells (37) and appears to be the "housekeeping" isoform of the catalytic subunit that maintains the low cytosolic Na ϩ concentration (7). In addition, astrocytes express the ␣2 isoform, whereas mature neurons express ␣3 (3,38,39). Thus, it is not surprising that IP of the detergent-soluble brain membrane fraction with an antibody to the ␣2 subunit of the Na ϩ pump co-IPs Ank 2 and ␣-fodrin, both of which are present in astrocytes, but not ␤-spectrin, which is not present (Fig.…”

Ionic Transporter Activity in Astrocytes, Microglia, and Oligodendrocytes During Brain Ischemia

“…134 The a1, a2, and a3 isoforms are expressed in the brain. 135 In particular, the a2 isoform is widely expressed in neurons during development 136 but becomes confined primarily to glia and few types of neurons in the adult brain; 134,137 in contrast, the a3 isoform shows neuronal expression in the adult. 134,137 Similar to the a subunit, the three b subunit isoforms are expressed to varying degrees in the brain, both in neurons and glia.…”