Aconitine (ACO) is a highly toxic diterpenoid alkaloid and known to exert the immunomodulatory action. However, whether it has any effects on ion currents in immune cells remains unknown. The effects of ACO and other related compounds on ion currents in Jurkat T-lymphocytes were investigated in this study. ACO suppressed the amplitude of delayed-rectifier K+ current (IK(DR)) in a time- and concentration-dependent manner. Margatoxin (100nM), a specific blocker of KV1.3-encoded current, decreased the IK(DR) amplitude in these cells and the ACO-induced inhibition of IK(DR) was not reversed by 1-ethyl-2-benzimidazolinone (30μM) or nicotine (10μM). The IC50 value for ACO-mediated inhibition of IK(DR) was 5.6μM. ACO accelerated the inactivation of IK(DR) with no change in the activation rate of this current. Increasing the ACO concentration not only reduced the IK(DR) amplitude, but also accelerated the inactivation time course of the current. With the aid of minimal binding scheme, the inhibitory action of ACO on IK(DR) was estimated with a dissociation constant of 6.8μM. ACO also shifted the inactivation curve of IK(DR) to a hyperpolarized potential with no change in the slope factor. Cumulative inactivation for IK(DR) was enhanced in the presence of ACO. In Jurkat cells incubated with amiloride (30μM), the ACO-induced inhibition of IK(DR) remained unaltered. In RAW 264.7 murine macrophages, ACO did not modify the kinetics of IK(DR), although it suppressed IK(DR) amplitude. Taken together, these effects can significantly contribute to its action on functional activity of immune cells if similar results are found in vivo.
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