کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4336263 | 1295203 | 2008 | 10 صفحه PDF | دانلود رایگان |

Changes in spontaneous spike activities from murine frontal cortex networks grown on microelectrode arrays were used to determine the dissociation constants of three GABAA antagonists: gabazine, bicuculline, and trimethylolpropane phosphate (TMPP). Networks were treated with fixed concentrations of antagonists and titrated with the GABAA receptor agonist muscimol. Muscimol decreased spike activity in a concentration-dependent manner with full efficacy (100% spike inhibition). A sigmoidal curve fit provided a 50% inhibitory concentration (IC50) of 0.14 ± 0.05 μM (mean ± S.D., n = 5). Increasing concentrations of the three antagonists shifted the muscimol concentration response curves (CRCs) to the right with the same efficacy. Schild plot analyses with linear regressions resulted in slopes that are statistically not different from unity and provided X-intercepts (dissociation constants) of 0.23, 0.61, and 3.98 μM for gabazine, bicuculline, and TMPP, respectively. Corresponding pA2 values (−log KB) were 6.64, 6.21, and 5.40. The dissociation constants for gabazine and bicuculline agree well with those obtained with other methods. The TMPP KB has not yet been reported in the literature. The data suggest that spontaneously active networks on microelectrode arrays can be used as reliable platforms for rapid quantitative pharmacological investigations.
Journal: Journal of Neuroscience Methods - Volume 173, Issue 2, 30 August 2008, Pages 183–192