{'fraction_non_alphanumeric': 0.031228784792939578, 'fraction_numerical': 0.020366598778004074, 'mean_word_length': 5.19327731092437, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
High‐affinity copper block of GABAA receptor‐mediated currents in acutely isolated cerebellar Purkinje cells of the rat

The actions of Cu2+ ions on GABAA receptor‐mediated currents in acutely isolated Purkinje cells from rat cerebellum were studied using the whole‐cell patch‐clamp technique and a rapid perfusion system. Bath application of Cu2+ reduced currents induced by 2 μmγ‐aminobutyric acid (GABA) in a concentration‐dependent manner with an IC50 of 35 n m. The Cu2+‐induced block of GABA responses was not voltage‐dependent. Increasing the GABA concentration (from 2 to 50 μm) decreased the blocking effect of Cu2+. Dose–response analysis for activation of GABAA receptors revealed a twofold decrease in apparent affinity for GABA in the presence of 0.1 μm Cu2+. Recovery from the block required several minutes after removal of Cu2+ from the medium. The block was removed by histidine, which preferentially forms complexes with Cu2+, or by other chelating substances. Application of 10 μm histidine immediately before application of 2 μm GABA completely relieved the block of GABA responses produced by 0.1 μm Cu2+. The effect of histidine was concentration‐dependent with an EC50 of 0.75 μm. The results demonstrate that Cu2+ is a potent inhibitor of GABA‐evoked responses in rat Purkinje cells. Copper may be an endogenous synaptic modulating factor. Cu2+ toxicity, notably in Wilson’s disease, could result to some extent from chronic GABAA receptor blockade.