Hypericin Activates L-Type Ca2+ Channels in Cardiac Myocytes
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- 作者：Martin-Pierre Sauviat ; Anthony Colas ; Marie-Jeanne Chauveau ; Jean-Claude Drapier ; Michel Né ; grerie
- 刊名：Journal of Natural Products
- 出版年：2007
- 出版时间：April 2007
- 年：2007
- 卷：70
- 期：4
- 页码：510 - 514
- 全文大小：80K
- 年卷期：v.70,no.4(April 2007)
- ISSN：1520-6025
文摘
The effects and the mode of action of hypericin (1) were studied, in the dark, on the action potential (AP) and theL-type Ca2+ channel of frog atrial heart muscle, using intracellular microelectrode and patch-clamp techniques,respectively. In the presence of Ca2+ in Ringer solution, hypericin (1 to 4 
M) did not markedly modify the AP. Totalreplacement of Ca2+ by Sr2+ in the solution (Ringer Sr2+) revealed that hypericin (4 M) prolonged the AP duration(APD). Hypericin dose-dependently increased the magnitude of the Sr2+current, which develops through L-type Ca2+channels in the Ringer solution containing tetrodotoxin (0.7 M) and tetraethylammonium (10 mM), but did not modifythe kinetics of activation and inactivation. This revealed that hypericin increased L-type Ca2+ channel conductance,which accounted for the APD lengthening. The hypericin-induced APD lengthening recorded in the Ringer Sr2+ wasnot prevented by (i) a blockade of 
- and 
-adrenoceptors by yohimbine (1 M), urapidil (1 M), and propanolol (50M), respectively, and (ii) PKC blockade by staurosporine (1 M). The hypericin-induced APD lengthening recordedin the Ringer Sr2+ was prevented by blocking soluble guanylate cyclase (sGC) activity by 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (13 M), which mimicked the effects of hypericin. Hypericin decreased the cellular cGMP level by69% in atrial myocytes. The compound also decreased the cellular cGMP level by inhibiting sGC, thus cancelling thenucleotide inhibitory effect on the cardiac L-type Ca2+ channel.
M) did not markedly modify the AP. Totalreplacement of Ca2+ by Sr2+ in the solution (Ringer Sr2+) revealed that hypericin (4 M) prolonged the AP duration(APD). Hypericin dose-dependently increased the magnitude of the Sr2+current, which develops through L-type Ca2+channels in the Ringer solution containing tetrodotoxin (0.7 M) and tetraethylammonium (10 mM), but did not modifythe kinetics of activation and inactivation. This revealed that hypericin increased L-type Ca2+ channel conductance,which accounted for the APD lengthening. The hypericin-induced APD lengthening recorded in the Ringer Sr2+ wasnot prevented by (i) a blockade of - and -adrenoceptors by yohimbine (1 M), urapidil (1 M), and propanolol (50M), respectively, and (ii) PKC blockade by staurosporine (1 M). The hypericin-induced APD lengthening recordedin the Ringer Sr2+ was prevented by blocking soluble guanylate cyclase (sGC) activity by 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (13 M), which mimicked the effects of hypericin. Hypericin decreased the cellular cGMP level by69% in atrial myocytes. The compound also decreased the cellular cGMP level by inhibiting sGC, thus cancelling thenucleotide inhibitory effect on the cardiac L-type Ca2+ channel.