Toosendanin, a triterpenoid derivative, acts as a novel agonist of L-type Ca2+channels in neonatal rat ventricular cells

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Abstract

Toosendanin, a triterpenoid derivative extracted from Melia toosendan Sieb et Zucc, was demonstrated to be potentially useful in medical and scientific researches. Here, we investigated the effects of toosendanin on L-type voltage-dependent Ca2+channels in cultured neonatal rat ventricular cells, using whole-cell patch-clamp method. Toosendanin irreversibly increased L-type Ca2+current (ICa(L)) in a concentration-dependent manner and shifted the maximum of the current/voltage relationship from 8.3±3.7 to 1.7±3.7 mV, without modifying the threshold potential of the current. Toosendanin shifted the steady-state activation and inactivation curves to the left. The deactivation kinetics of the ICa(L)was significantly slowed by toosendanin while the activation kinetics was not affected. The cells pretreated with 100 nM 1,4-dihydro-2,6-dimethyl-5-nitro-4- [2-(trifluoromethyl)phenyl]-3-pyridinecarboxylic acid methyl ester (S(-)-BayK8644) still respond to further addition of 87 μM toosendanin, and vice versa. These results prove toosendanin to be a novel L-type Ca2+channel agonist, which possesses a distinct binding site from BayK8644. © 2004 Elsevier B.V. All rights reserved.

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Li, M. F., & Shi, Y. L. (2004). Toosendanin, a triterpenoid derivative, acts as a novel agonist of L-type Ca2+channels in neonatal rat ventricular cells. European Journal of Pharmacology, 501(1–3), 71–78. https://doi.org/10.1016/j.ejphar.2004.08.027

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