The Expression and Phosphorylation of Acid Sensing Ion Channel 1a in the Brain of a Mouse Model of Phenylketonuria

ABSTRACT

The acid-sensing ion channel 1a (ASIC1a) is a proton-gated cation channel enriched in the mammalian brain. Recent studies suggest its diverse roles in ischemic acidosis, neurodegenerative diseases, and cognitive processes. Phenylketonuria (PKU) is the most commonly inherited defect in amino acid metabolism. Many facts make ASIC1a appear to be highly related to PKU. In this study, we explored the effect of PKU on the expression and serine phosphorylation of ASIC1a in a mouse model of PKU, BTBR-Pah^enu2. Genotyping was performed by blood phenylalanine (Phe) determination and gene analysis. ASIC1a mRNA, ASIC1a protein, and serine phosphorylated ASIC1a (pSer-ASIC1a) in the cerebral cortex and hippocampus were detected by real-time polymerase chain reaction (PCR), Western blot, and immunoprecipitation, respectively. The expression of ASIC1a mRNA and protein in the two encephalic regions showed no difference between wild type (WT) and PKU mice. In the hippocampus of the 2-week-old (2W) PKU mice, pSer-ASIC1a was increased compared to WT mice. These data suggest that PKU-related brain injury is independent of ASIC1a expression. Serine phosphorylation of ASIC1a, however, may be involved.

KEYWORDS: :

• Acid sensing ion channel 1a
• brain injury
• expression
• Pah^enu2 mouse model
• phenylketonuria
• phosphorylation