Influence of phenylalanine and its derivatives on intracellular free calcium of embryonic rat cortical neurons

    ZHANG Huiª²Wen, YUAN Xiaoª²Bing, ZHANG Yongª²Jun, GU Xueª²Fan

    1Department of Pediatric Endocrinology & Genetic Metabolism, Xinhua Hospital, Shanghai Second Medical University, Shanghai Institute for Pediatric Research, Shanghai 200092, China, 2Institute of Neuroscience, Shanghai Academy of Biological Sciences, Chinese Academy of Science, Shanghai 200031, China

    ¡¾Abstract¡¿ AIM: To gain more insight into the mechanism of neuronal injury in phenylketonuria patients and to investigate the effect of phenylalanine on intracellular free calcium concentration ([Ca]i) of embryonic rat cortical neurons. METHODS: Calcium imaging was used to observe the influence of Lª²phenylalanine and its derivatives on [Ca]i. RESULTS: High concentration of Lª²phenylalanine (Phe, 10 mmol/L) and DLª²¦Âª²phenyllactic acid (PL,10 mmol/L)decreased [Ca]i, while phenylacetic acid (PAA, 10 mmol/L) decreased, then increased, and again decreased [Ca]i. With the normal extracellular balance solution replaced by calciumª²free and natriumª²free balance solution, PL did not change its effect on intracellular free calcium. With Thapsigargin (100 nmol/L) added to the normal extracellular solution to inhibit the sarcoplasmic/endoplasmic reticulum Ca2+ª²ATPase(SERCA), PAA decreased [Ca]i, and no subsequent increase of [Ca]i was observed. With the same concentration, PL and PAA had more significant effects on immature neurons. CONCLUSION: Combining the result of gene chips, Lª²phenylalanine and its derivatives can activate plasma membrane Ca2+ª²ATPase and accelerate the extrusion of intracellular free calcium from neurons, thus resulting in the decrease of [Ca]i. ......