Midazolam's Effects on Delayed-Rectifier K <superscript>+</superscript> Current and Intermediate-Conductance Ca <superscript>2+</superscript> -Activated K <superscript>+</superscript> Channel in Jurkat T-lymphocytes. - OpacWWW

Tytuł:: Midazolam's Effects on Delayed-Rectifier K Channel in Jurkat T-lymphocytes.
Autorzy:: Foo NP; Department of Emergency Medicine, An Nan Hospital, China Medical University, Tainan City 709204, Taiwan.; Graduate Institute of Medical Sciences, Chang Jung Christian University, Tainan City 711301, Taiwan.
Liu YF; Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei City 100233, Taiwan.
Wu PC; Department of Biomedical Engineering, National Cheng Kung University, Tainan City 70101, Taiwan.; Institute of Oral Medicine and Department of Stomatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City 704302, Taiwan.; Center of Applied Nanomedicine, National Cheng Kung University, Tainan City 70101, Taiwan.; Medical Device Innovation Center, Taiwan Innovation Center of Medical Devices and Technology, National Cheng Kung University Hospital, National Cheng Kung University, Tainan City 704302, Taiwan.
Hsing CH; Department of Anesthesia, Chi Mei Medical Center, Tainan City 710402, Taiwan.
Huang BM; Department of Cell Biology and Anatomy, National Cheng Kung University, Tainan City 70101, Taiwan.; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404332, Taiwan.
So EC; Graduate Institute of Medical Sciences, Chang Jung Christian University, Tainan City 711301, Taiwan.; Department of Anesthesia & Medical Research, An Nan Hospital, China Medical University, Tainan City 709204, Taiwan.
Źródło:: International journal of molecular sciences [Int J Mol Sci] 2021 Jul 04; Vol. 22 (13). Date of Electronic Publication: 2021 Jul 04.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Original Publication: Basel, Switzerland : MDPI, [2000-
MeSH Terms:: Delayed Rectifier Potassium Channels/*antagonists & inhibitors
Intermediate-Conductance Calcium-Activated Potassium Channels/*antagonists & inhibitors
Midazolam/*pharmacology
T-Lymphocytes/*drug effects
T-Lymphocytes/*metabolism
Animals ; Cytokines/metabolism ; Delayed Rectifier Potassium Channels/metabolism ; Dose-Response Relationship, Drug ; Flumazenil/pharmacology ; GABA-A Receptor Antagonists/pharmacology ; Humans ; Hypnotics and Sedatives/administration & dosage ; Hypnotics and Sedatives/pharmacology ; Intermediate-Conductance Calcium-Activated Potassium Channels/metabolism ; Jurkat Cells ; Kinetics ; Lipopolysaccharides/pharmacology ; Lymphocyte Activation ; Microscopy, Confocal ; Midazolam/administration & dosage ; Patch-Clamp Techniques ; Phytohemagglutinins/pharmacology ; T-Lymphocytes/immunology
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Grant Information:: ANHRF2019-03 An Nan Hospital, China Medical University
Contributed Indexing:: Keywords: delayed-rectifier K+ current; inactivation kinetics; interleukin; intermediate-conductance Ca2+-activated K+ channel; lymphocyte; midazolam
Substance Nomenclature:: 0 (Cytokines)
0 (Delayed Rectifier Potassium Channels)
0 (GABA-A Receptor Antagonists)
0 (Hypnotics and Sedatives)
0 (Intermediate-Conductance Calcium-Activated Potassium Channels)
0 (Lipopolysaccharides)
0 (Phytohemagglutinins)
40P7XK9392 (Flumazenil)
R60L0SM5BC (Midazolam)
Entry Date(s):: Date Created: 20210720 Date Completed: 20210727 Latest Revision: 20210727
Update Code:: 20240105
PubMed Central ID:: PMC8267671
DOI:: 10.3390/ijms22137198
PMID:: 34281255
: Czasopismo naukowe

Pełny tekst

Midazolam (MDZ) could affect lymphocyte immune functions. However, the influence of MDZ on cell's K + currents has never been investigated. Thus, in the present study, the effects of MDZ on Jurkat T lymphocytes were studied using the patch-clamp technique. Results showed that MDZ suppressed the amplitude of delayed-rectifier K + current ( I K(DR) ) in concentration-, time-, and state-dependent manners. The IC 50 for MDZ-mediated reduction of I K(DR) density was 5.87 μM. Increasing MDZ concentration raised the rate of current-density inactivation and its inhibitory action on I K(DR) density was estimated with a dissociation constant of 5.14 μM. In addition, the inactivation curve of I K(DR) associated with MDZ was shifted to a hyperpolarized potential with no change on the slope factor. MDZ-induced inhibition of I K(DR) was not reversed by flumazenil. In addition, the activity of intermediate-conductance Ca 2+ -activated K + (IK Ca ) channels was suppressed by MDZ. Furthermore, inhibition by MDZ on both I K(DR) and IK Ca -channel activity appeared to be independent from GABAA receptors and affected immune-regulating cytokine expression in LPS/PMA-treated human T lymphocytes. In conclusion, MDZ suppressed current density of I K(DR) in concentration-, time-, and state-dependent manners in Jurkat T-lymphocytes and affected immune-regulating cytokine expression in LPS/PMA-treated human T lymphocytes.

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Informacja

Midazolam's Effects on Delayed-Rectifier K + Current and Intermediate-Conductance Ca 2+ -Activated K + Channel in Jurkat T-lymphocytes.