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

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 () in concentration-, time-, and state-dependent manners. The IC for MDZ-mediated reduction of density was 5.87 μM. Increasing MDZ concentration raised the rate of current-density inactivation and its inhibitory action on density was estimated with a dissociation constant of 5.14 μM. In addition, the inactivation curve of associated with MDZ was shifted to a hyperpolarized potential with no change on the slope factor. MDZ-induced inhibition of was not reversed by flumazenil. In addition, the activity of intermediate-conductance Ca-activated K (IK) channels was suppressed by MDZ. Furthermore, inhibition by MDZ on both and IK-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 in concentration-, time-, and state-dependent manners in Jurkat T-lymphocytes and affected immune-regulating cytokine expression in LPS/PMA-treated human T lymphocytes.