Midazolam’s Effects on Delayed-Rectifier K(+) Current and Intermediate-Conductance Ca(2+)-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 (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.