Toosendanin, a triterpenoid derivative, acts as a novel agonist of L-type Ca2+ channels in neonatal rat ventricular cells.
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 Ca(2+) channels in cultured neonatal rat ventricular cells, using whole-cell patch-clamp method. Toosendanin irreversibly increased L-type Ca(2+) current (I(Ca(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 I(Ca(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 microM toosendanin, and vice versa. These results prove toosendanin to be a novel L-type Ca(2+) channel agonist, which possesses a distinct binding site from BayK8644.
Key Laboratory of Neurobiology, Institute of Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, P.R. China.
Mu-Feng
MF
Li
Yu-Liang
YL
Shi
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014315:Triterpenes / Q000494:pharmacology*; D016276:Ventricular Function
D002120:Calcium Channel Agonists; D020746:Calcium Channels, L-Type; D004365:Drugs, Chinese Herbal; D014315:Triterpenes; C036454:toosendanin