Blockade of AMPA receptors by nickel in cultured rat astrocytes

✍ Scribed by Petra Telgkamp; Kurt H. Backus; Joachim W. Deitmer

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 784 KB
• Volume: 16
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/(sici)1098-1136(199602)16:2<140::aid-glia6>3.0.co;2-7

✦ Synopsis

The effect of NiLt on glial a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors was studied using the whole-cell patch-clamp technique in cultured rat cerebellar astrocytes. The application of kainate (10 pM-5 mM) evoked inward currents at a holding potential of -70 mV. These currents were blocked by 6cyano-7-nitroquinoxaline-2,3-dione (CNQX) and Evans Blue, and potentiated by cyclothiazide, suggesting that they were primarily mediated by the AMPA receptor subtype. Analysis of the kainate concentration-response relation in cultured astrocytes revealed a maximal current of 488 PA, a half-maximal effective concentration of 137 p M and a Hill coefficient of 1.43, indicating more than one agonist binding site. N P inhibited the current activated by 300 pM kainate in a concentration-dependent manner, displaying a half-maximal inhibition at 860 pM Ni" and a Hill coefficient of 1.07. In the presence of 700 pM Ni2+ the kainate-induced concentration-response curve was shifted towards higher concentrations, increasing the half-maximal effective concentration to 300 pM, without significantly changing the Hill coefficient. The blocking effect of Ni2+ was counteracted by increasing kainate concentrations, suggesting a competitive mechanism.