Analysis of GABAA- and GABAB-receptor mediated effects on intracellular Ca2+ in DRG hybrid neurones

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Abstract

1. Using pharmacological analysis and fura-2 spectrofluorimetry, we examined the effects of γ-aminobutyric acid (GABA) and related substances on intracellular Ca2+ concentration ([Ca2+]i) of hybrid neurones, called MD3 cells. The cell line was produced by fusion between a mouse neuroblastoma cell and a mouse dorsal root ganglion (DRG) neurone. 2. MD3 cells exhibited DRG neurone-like properties, such as immunoreactivity to microtubule-associated protein-2 and neurofilament proteins. Bath applications of capsaicin and α, β-methylene adenosine triphosphate reversibly increased [Ca2+]i. However, repeated applications of capsaicin were much less effective. 3. Pressure applications of GABA (100 μM), (Z)-3-[(aminoiminomethyl) thio] prop-2-enoic acid sulphate (ZAPA; 100 μM), an agonist at low affinity GABAA-receptors, or KCl (25 mM), transiently increased [Ca2+]i. 4. Bath application of bicuculline (100 nM - 100 μM), but not picrotoxinin (10 - 25 μM), antagonized GABA-induced increases in [Ca2+]i in a concentration-dependent manner (IC50 = 9.3 μM). 5. Ca2+-free perfusion reversibly abolished GABA-evoked increases in [Ca2+]i. Nifedipine and nimodipine eliminated GABA-evoked increases in [Ca2+]i. These results imply GABA response dependence on extracellular Ca2+. 6. Baclofen (500 nM - 100 μM) activation of GABAB-receptors reversibly attenuated KCl-induced increases in [Ca2+]i in a concentration-dependent manner (EC50= 1.8 μM). 2-hydroxy-saclofen (1 - 20 μM) antagonized the baclofen-depression of the KCl-induced increase in [Ca2+]i. 7. In conclusion, GABAA-receptor activation had effects similar to depolarization by high external K+, initiating Ca2+ influx through high voltage-activated channels, thereby transiently elevating [Ca2+]i. GABAB-receptor activation reduced Ca2+ influx evoked by depolarization, possibly at Ca2+-channel sites in MD3 cells.

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Yokogawa, T., Kim, S. U., Krieger, C., & Puil, E. (2001). Analysis of GABAA- and GABAB-receptor mediated effects on intracellular Ca2+ in DRG hybrid neurones. British Journal of Pharmacology, 134(1), 98–107. https://doi.org/10.1038/sj.bjp.0704244

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