Abstract
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 (IK(DR)) in concentration-, time-, and state-dependent manners. The IC50 for MDZ-mediated reduction of IK(DR) density was 5.87 μM. Increasing MDZ concentration raised the rate of current-density inactivation and its inhibitory action on IK(DR) density was estimated with a dissociation constant of 5.14 μM. In addition, the inactivation curve of IK(DR) associated with MDZ was shifted to a hyperpolarized potential with no change on the slope factor. MDZ-induced inhibition of IK(DR) was not reversed by flumazenil. In addition, the activity of intermediate-conductance Ca2+-activated K+ (IKCa) channels was suppressed by MDZ. Furthermore, inhibition by MDZ on both IK(DR) and IKCa-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 IK(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.
Highlights
Midazolam (MDZ) is a common sedative drug for patients during procedures and surgery
This study aimed to evaluate the effects of MDZ on ionic currents in Jurkat Tlymphocytes and in phytohemagglutinin (PHA)-preactivated human T lymphocytes, at IK(DR) and IKCa channels
The nucleus was stained with DAPI to show blue color while Alexa and Fluorescein isothiocyanate (FITC) were found on the cell membrane
Summary
Midazolam (MDZ) is a common sedative drug for patients during procedures and surgery. KV1.3 and Kv1.5-encoded currents, which exhibit unique gating properties and voltage dependency, largely constitute the delayed-rectifier K+ currents (IK(DR) in immune cells [3,16,17,18]. These currents, which can be functionally expressed in the plasma membrane and the inner mitochondrial membrane, have been demonstrated to perform key functions in the immune system, such as lymphocyte activation [3,15,18,19,20,21,22,23,24]
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