Ketamine (KT), a dissociative anesthetic, is known to induce schizophrenia-like psychosis. The percentage of KT abuse has recently grown fast despite KT being a controlled drug. The mechanism of KT actions is related to the inhibition of NMDA receptors. Whether KT produces other effects on ion currents in hippocampal neurons remains unclear. In this study, we attempted to evaluate the possible effects of KT and other related compounds on ion currents in hippocampal neuron-derived H19-7 cells. This drug exerted an inhibitory effect on Ca(2+)-activated K(+) current (IK(Ca)) in these cells with an IC(50) value of 274 μM. Pimaric acid (30 μM) or abietic acid (30 μM), known to stimulate large-conductance Ca(2+)-activated K(+) channels, reversed KT-induced inhibition of I(K)(Ca). In HEK293T cells expressing a-humans low poke, KT-induced inhibition of I(K)(Ca) still existed. Dehydronorketamine (300 μM) had little or no effect on the IK(Ca) amplitude, while norketamine (300 μM) slightly but significantly suppressed it. In inside–out configuration, KT applied to the intracellular face of the membrane did not alter single channel conductance of large-conductance Ca(2+)-activated K(+) (BKCa) channels; however, it did significantly reduce the probability of channel openings. Addition of KT was effective in depressing the peak amplitude of voltage-gated Na(+) current. Moreover, the presence of KT was noted to enhance the amplitude of membrane electroporation-induced inward currents (IMEP) in differentiated H19-7 cells. KT-stimulated IMEP was reversed by further application of LaCl(3) (100 μM), but not by NMDA (30 μM). The modulations by this compound of ion channels may contribute to the underlying mechanisms through which KT and its metabolites influence the electrical behavior of hippocampal neurons if similar findings occur in vivo.

中文翻译：

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氯胺酮及其代谢物对分化的海马H19-7神经元细胞和转染α-hslo亚基的HEK293T细胞离子电流的影响。

氯胺酮（KT）是一种解离性麻醉药，可诱发精神分裂症样精神病。尽管KT是受管制的药物，但最近KT滥用的百分比增长迅速。KT作用的机制与抑制NMDA受体有关。KT是否会对海马神经元的离子电流产生其他影响尚不清楚。在这项研究中，我们试图评估KT和其他相关化合物对海马神经元衍生的H19-7细胞离子电流的可能影响。该药物对这些细胞中的Ca（2+）激活的K（+）电流（IK（Ca））具有抑制作用，IC（50）值为274μM。已知会刺激大电导Ca（2+）激活的K（+）通道的香豆酸（30μM）或松香酸（30μM）逆转了KT诱导的I（K）（Ca）抑制作用。在表达a-人类低p的HEK293T细胞中，KT诱导的I（K）（Ca）抑制作用仍然存在。脱氢去甲氯胺酮（300μM）对IK（Ca）振幅影响很小或没有影响，而去甲去甲胺（300μM）略微但显着抑制了它。在由内而外的配置中，将KT应用于膜的细胞内表面并不会改变大电导Ca（2+）激活的K（+）（BKCa）通道的单通道电导。但是，它确实降低了渠道开放的可能性。添加KT可有效降低电压门控Na（+）电流的峰值幅度。此外，注意到KT的存在可增强分化的H19-7细胞中膜电穿孔诱导的内向电流（IMEP）的幅度。通过进一步应用LaCl（3）（100μM），而不是NMDA（30μM），可逆转KT刺激的IMEP。