The inhibitory effect of IL-6/IL-6R on TRPM7 currents is blocked by the JAK2 inhibitor AG490, but not by inhibitors of PI3K and PLC.

<p>(A) Currents recorded when cells were perfused with divalent ion-free extracellular solution, IL-6/sIL-6R, AG490, or AG490 combined with IL-6/sIL-6R, respectively. (B) The inhibitory role of IL-6 on TRPM7 inward currents could be blocked by the JAK2 inhibitor AG490 (n = 11) (C) Current traces recorded with perfusion of divalent ion-free extracellular solution, IL-6/sIL-6R, wortmannin, or wortmannin combined with IL-6/sIL-6R, respectively. (D) Relative currents normalized to the TRPM7 current at -100 mV and recorded during perfusion of divalent ion-free extracellular solution. The specific PI3K inhibitor wortmannin did not block the effect of IL-6 on TRPM7 inward currents at -100 mV (n = 6). (E) Current traces recorded during perfusion of divalent ion-free extracellular solution, IL-6/sIL-6R, U73122, or U73122 combined with IL-6/sIL-6R, respectively. (F) Relative currents normalized to TRPM7 currents recorded with perfusion of divalent ion-free extracellular solution. The PLC inhibitor U73122 inhibited TRPM7 inward currents at -100 mV, but did not block the effects of IL-6/sIL-6R (n = 7, * p < 0.05 vs. control, # p < 0.05 vs. IL-6/sIL-6R). All currents were normalized to controls (perfusion with divalent ion-free extracellular solution) at -100 mV.