Abstract:
: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 (I(K(DR))) in a time- and concentration-dependent manner. Margatoxin (100 nM), a specific blocker of K(V)1.3-encoded current, decreased the I(K(DR)) amplitude in these cells and the ACO-induced inhibition of I(K(DR)) was not reversed by 1-ethyl-2-benzimidazolinone (30 μM) or nicotine (10 μM). The IC(50) value for ACO-mediated inhibition of I(K(DR)) was 5.6 μM. ACO accelerated the inactivation of I(K(DR)) with no change in the activation rate of this current. Increasing the ACO concentration not only reduced the I(K(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 I(K(DR)) was estimated with a dissociation constant of 6.8 μM. ACO also shifted the inactivation curve of I(K(DR)) to a hyperpolarized potential with no change in the slope factor. Cumulative inactivation for I(K(DR)) was enhanced in the presence of ACO. In Jurkat cells incubated with amiloride (30 μM), the ACO-induced inhibition of I(K(DR)) remained unaltered. In RAW 264.7 murine macrophages, ACO did not modify the kinetics of I(K(DR)), although it suppressed I(K(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.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Wu SN,Chen BS,Lo YCdoi
10.1016/j.tox.2011.07.003subject
Has Abstractpub_date
2011-10-28 00:00:00pages
11-8issue
1eissn
0300-483Xissn
1879-3185pii
S0300-483X(11)00259-9journal_volume
289pub_type
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