Anti-Na⁺/H⁺ Exchanger 6 (NHE-6) Antibody

Intracellular pH regulation in the brain is extremely important in both physiological and pathophysiological conditions. Changes in Intracellular pH often result in altered neuronal excitability. In mammalian cells, intracellular pH against acidosis is generally regulated by ion transporters located on the plasma membrane called sodium-hydrogen exchangers (Na⁺/H⁺ exchanger, NHE)^1,2. In addition to their role in regulating pH, NHE transporters also function in a coupled mode to mediate recovery from decreased cell volume¹.

Several studies have suggested that Na⁺/H⁺ exchange is the predominant pH-regulatory mode in isolated nerve terminals. In addition, Na⁺/H⁺ exchange plays a role in regulating synaptic transmission at glutamatergic, GABAergic, and dopaminergic synapses¹.

The NHE family belongs to the Slc9 gene family of Na⁺ coupled transport proteins and comprises nine mammalian isoforms of Na⁺/H⁺ exchangers that are localized to the plasma membrane, NHE1-9 encoded by the SLC9A1-SLC9A9 genes, respectively. SLC9 family members have a short N terminus and an extensive C terminus that plays a regulatory role².

NHE6 is localized to early and recycling endosomes, where it exchanges luminal H⁺ for Na⁺ or K⁺. Its expression is highest in the spinal cord and brain and is particularly enriched in the hippocampus, cortex, and Purkinje cell layer of the cerebellum³. Mutations in NHE6 encoding gene have been linked to autism, Christianson syndrome, and Angelman-like syndrome.