Inhibition of Ca2+-Release–Activated Ca2+ Channel (CRAC) and K+ Channels by Curcumin in Jurkat-T Cells

Abstract

The increase in cytoplasmic Ca2+ concentration (Δ[Ca2+]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 (Kv) 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 (ICRAC), Kv (IKv), SK4 (ISK4) 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 ICRAC by curcumin was confirmed in Jurkat-T (IC50, 5.9 μM) and the HEK293 cells overexpressing Orai1 and STIM1 (IC50, 0.6 μM). Also, curcumin inhibited both IKv (IC50, 11.9 μM) and ISK4 (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.[Supplementary Figures: available only at http://dx.doi.org/10.1254/jphs.10209FP] Keywords:: curcumin, T cell, Ca2+-release–activated Ca2+ channel, K+ channel, polyphenol