Midazolam's Effects on Delayed-Rectifier K⁺ Current and Intermediate-Conductance Ca²⁺-Activated K⁺ Channel in Jurkat T-lymphocytes.

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 (I_K(DR)) in concentration-, time-, and state-dependent manners. The IC₅₀ 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 Ca²⁺-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.

SUBMITTER: Foo NP 

PROVIDER: S-EPMC8267671 | biostudies-literature |

REPOSITORIES: biostudies-literature