Table 1.—

The Cellular Locations, Effects of Gene Knockout, Known Human Mutations, and Functions of the 3 α, 3 β, and 5 γ Isoforms of Nkat That Are Found in the Brain

Isoform	Brain/cell location multiple isoforms in same cell	Effect from gene knockout	Human mutations	Function	Refs
α1	Neurons and glia	Homozygous die at blastocyst. Heterozygous normal		Catalytic, ion transport, phos-phorylation, and ATP binding. They differ in Na⁺, K⁺, and ATP binding, ouabain and Ca²⁺ inhibition. Eg, ouabain and ATP affinities are lowest for α1, highest for α2 and 3	^106–111
α2	Glial cells mainly, occasional neurons	Homozygous die at birth: ↓ breathing. Heterozygous have ↑ anxiety and ↓ long-term memory	FHM-2		^{106–109,111}
α3	Neurons	Homozygous die at birth. Heterozygous ↓ non-spatial learning and long-term memory	Rapid onset dystonia parkinsonism		^106–111
β1	Mainly neurons	Not known		Membrane insertion, protein:protein interactions, tight junctions, cell polarity, and signaling	^112,113
β2	Mainly glia	Deficient neural cell migration, die 15 d			^112–114
β3	Oligodendroglial cells and optic nerve	Not known			¹¹⁵
FXYD1	Combines with α1–3 in cerebellum. Most abundant in Purkinje cells, and choroid plexus and ependymal cells. In neurons and glia. Small amount in Allan Atlas rat brain^*.	↑ NKAT activity in heart		↓ Affinity of NKAT for Na⁺ and K⁺	^{46, 116–118}
FXYD2	Moderate amount in Allan Atlas rat brain^*.	↑ affinity of NKAT for Na⁺.	Renal hypo-magnesemia	↓ Affinity of NKAT for Na⁺	^46,119–121
FXYD3	None in Allan Atlas rat brain^*.	Not done		↓ Affinity of NKAT for Na⁺/K⁺	⁴⁶
FXYD4	None in Allan Atlas rat brain^*.	Not known in brain ↓ Na⁺ resorption			⁴⁶
FXYD5	Small amount in Allan Atlas rat brain^*.	Not done		↑ NKAT I_max	⁴⁶
FXYD6	Extensive, abundant expression in Allan Atlas rat brain^*. Cerebellum and hippocampus.	Not done		↓ Affinity of NKAT for Na⁺/K⁺	^46,122
FXYD7	Almost exclusive to brain. Extensive PTMs. Large amount in Allan Atlas rat brain^*.	Not done		↓ Affinity of NKAT for K⁺	^{46,87,123,124}

FHM = familial hemiplegic migraine; NKAT = Na+, K+ -ATPase transporter.