Cheikh Amani, Benkhalifa Rym, Bescond Jocelyn, El Ayeb Mohamed, Raymond Guy, Cognard Christian, Potreau Daniel
Laboratoire Venins et Toxines, Institut Pasteur de Tunis, BP 74-1002, Tunis, Tunisia.
Toxicon. 2006 Sep 15;48(4):373-87. doi: 10.1016/j.toxicon.2006.06.016. Epub 2006 Jul 4.
The effects of a non-toxic fraction, called M1, from Buthus occitanus tunetanus (Bot) scorpion were studied on rat cardiac contraction and calcium transient and current. A decrease in both rate and tension on isolated intact hearts as well as in calcium transient induced by depolarizing 100 K(+) solution on isolated ventricular cardiomyocytes was firstly observed. Studies with the whole cell patch clamp method showed that M1 decreased the L-type calcium current (ICa(L)) in a dose-dependent manner with an IC50 of 0.36 microg/mL and a Hill coefficient of 0.95. This effect was blocked and reversed by the specific muscarinic receptors antagonist atropine, 1 microM, and was completely prevented when cardiomyocytes were pretreated with Pertussis toxin, 1 microg/mL, to block the alpha subunit of the PTX-sensitive G proteins. These results show that M1 fraction of Bot inhibits basal calcium current by interacting with muscarinic receptors and suggest that this inhibition could be attributed to inhibition of adenylate cyclase activity by a mechanism involving PTX-sensitive G proteins.
研究了来自突尼斯金蝎（Buthus occitanus tunetanus，Bot）的一种名为M1的无毒组分对大鼠心脏收缩、钙瞬变和电流的影响。首先观察到，在离体完整心脏上，速率和张力均降低，在离体心室心肌细胞上，由100 K(+) 去极化溶液诱导的钙瞬变也降低。采用全细胞膜片钳法进行的研究表明，M1以剂量依赖方式降低L型钙电流（ICa(L)），IC50为0.36微克/毫升，希尔系数为0.95。1微摩尔的特异性毒蕈碱受体拮抗剂阿托品可阻断并逆转这种效应，当心肌细胞用1微克/毫升百日咳毒素预处理以阻断PTX敏感G蛋白的α亚基时，这种效应被完全阻止。这些结果表明，Bot的M1组分通过与毒蕈碱受体相互作用抑制基础钙电流，并表明这种抑制可能归因于通过涉及PTX敏感G蛋白的机制抑制腺苷酸环化酶活性。
