Document Detail


Effects of ketamine and its metabolites on ion currents in differentiated hippocampal H19-7 neuronal cells and in HEK293T cells transfected with α-hslo subunit.
MedLine Citation:
PMID:  23227486     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
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.
Authors:
Mei-Han Huang; Kuan-Hua Lin; Sheue-Jiun Chen; Ai-Yu Shen; Fang-Tzu Wu; Sheng-Nan Wu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neurotoxicology     Volume:  33     ISSN:  1872-9711     ISO Abbreviation:  Neurotoxicology     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-12-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7905589     Medline TA:  Neurotoxicology     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1058-66     Citation Subset:  IM    
Affiliation:
Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Sciences, Fooyin University, Ta-Liao District, Kaohsiung city, Taiwan.
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