Abstract：
:The effects of divalent and trivalent cations on the gamma-aminobutyric acid (GABA)-induced chloride current were studied with rat dorsal root ganglion neurons in primary culture using the whole-cell configuration of the patch-clamp technique. Lanthanum (La3+) reversibly potentiated the GABA-induced current with a half-maximal effective concentration (EC50) of 231 microM and the maximal potentiation to about 300% of control. La3+ did not seem to compete with chlordiazepoxide, pentobarbital or picrotoxin for binding sites, which indicated that the La3+ binding site was distinct from any of the benzodiazepine, barbiturate and picrotoxin binding sites on the GABA receptor-channel complex. Copper (Cu2+) reversibly suppressed the current induced by GABA with an EC50 of 19 microM in a non-competitive manner. Zinc (Zn2+) and Cu2+ had a very similar action on GABA response in terms of potency and efficacy. The degree of suppression of GABA-induced current by Cu2+ and Zn2+ was not affected by La3+, whereas Cu2+ antagonized the blocking action of Zn2+ in a concentration-dependent manner. Therefore, La3+ does not interfere with the binding site(s) for Cu2+ and Zn2+, whereas Cu2+ and Zn2+ may share a common site. These results are consistent with the presence of at least two distinct binding sites for polyvalent cations on the GABA-receptor channel complex: one for positive regulation by La3+ and the other for negative regulation by Cu2+ and Zn2+. These two sites are likely to be located at or near the external orifice of the chloride channel.
journal_name
Brain Resjournal_title
Brain researchauthors
Ma JY,Narahashi Tdoi
10.1016/0006-8993(93)91510-ysubject
Has Abstractpub_date
1993-04-02 00:00:00pages
222-32issue
1-2eissn
0006-8993issn
1872-6240pii
0006-8993(93)91510-Yjournal_volume
607pub_type
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