Inhibition of Ca²⁺-release-activated Ca²⁺ channel (CRAC) and K⁺ channels by curcumin in Jurkat-T cells

The increase in cytoplasmic Ca²⁺ concentration (Δ[Ca ²⁺]_c) mediated by the Ca²⁺-release-activated Ca²⁺ channel (CRAC) is a critical signal for the activation of lymphocytes. Also, the voltage-gated K⁺ channel (K_v) and intermediate-conductance Ca²⁺-activated K⁺ channel (IKCa1/SK4) have drawn attention as pharmacological targets for regulating immune responses. Since polyphenolic agents have various immunomodulatory effects, here we compared the effects of curcumin, rosmarinic acid, resveratrol, and epigallocatechin gallate on the ionic currents through CRAC (I _CRAC), K_v (I_Kv), SK4 (I_SK4) and on the Δ[Ca²⁺]_c of Jurkat-T cells using the patch clamp technique and fura-2 spectrofluorimetry. Curcumin (10 μM) inhibited store-operated Ca²⁺ entry (SOCE). Consistently, dose-dependent inhibition of I_CRAC by curcumin was confirmed in Jurkat-T (IC50, 5.9 μM) and the HEK293 cells overexpressing Orai1 and STIM1 (I_C50, 0.6 μM). Also, curcumin inhibited both I_Kv (IC₅₀, 11.9 μM) and I_SK4 (IC₅₀, 4.2 μM). The other polyphenols (rosmarinic acid, resveratrol, and epigallocatechin gallate at 10-30 μM) had no effect on SOCE and showed only a partial inhibition of the K⁺ currents. In summary, among the tested polyphenolic agents, curcumin showed prominent inhibition of major ion channels in lymphocytes, which might contribute to the anti-inflammatory effects of curcumin.