Posgrado en Ciencias del Mar y Limnología, Universidad Nacional Autónoma de México, Circuito Exterior S/N, Ciudad Universitaria, C.P. 04510, Coyoacán, Mexico, Mexico.
Unidad Académica de Sistemas Arrecifales Puerto Morelos, Instituto de Ciencias del Mar y Limnología, Universidad Nacional Autónoma de México, Prolongación Niños Héroes s/n, Domicilio Conocido, C.P. 77580, Puerto Morelos, Quintana Roo, Mexico.
Sci Rep. 2022 Mar 30;12(1):5352. doi: 10.1038/s41598-022-09339-x.
Toxin production in nematocysts by Cnidaria phylum represents an important source of bioactive compounds. Using electrophysiology and, heterologous expression of mammalian ion channels in the Xenopus oocyte membrane, we identified two main effects produced by the sea anemone Bartholomea annulata venom. Nematocysts isolation and controlled discharge of their content, revealed that venom had potent effects on both voltage-dependent Na (Na) channels and GABA type A channel receptors (GABAR), two essential proteins in central nervous system signaling. Unlike many others sea anemone toxins, which slow the inactivation rate of Na channels, B. annulata venom potently inhibited the neuronal action potential and the Na currents generated by distinct Na channels opening, including human TTX-sensitive (hNa1.6) and TTX-insensitive Na channels (hNa1.5). A second effect of B. annulata venom was an agonistic action on GABAR that activated distinct receptors conformed by either α1β2γ2, α3β2γ1 or, ρ1 homomeric receptors. Since GABA was detected in venom samples by ELISA assay at low nanomolar range, it was excluded that GABA from nematocysts directly activated the GABARs. This revealed that substances in B. annulata nematocysts generated at least two potent and novel effects on mammalian ion channels that are crucial for nervous system signaling.
刺胞动物门的刺丝囊产生毒素，这是生物活性化合物的重要来源。我们使用电生理学和在非洲爪蟾卵母细胞膜中异源表达哺乳动物离子通道的方法，鉴定了来自海葵 Bartholomea annulata 的毒液的两种主要作用。刺丝囊的分离和内容物的受控释放表明，毒液对电压依赖性 Na (Na) 通道和 GABA 型 A 通道受体 (GABAR) 都有很强的作用，这两种蛋白都是中枢神经系统信号传导中的重要蛋白。与许多其他海葵毒素不同，这些毒素会减缓 Na 通道的失活速度，B. annulata 毒液强烈抑制神经元动作电位和由不同 Na 通道开放产生的 Na 电流，包括人类 TTX 敏感型 (hNa1.6) 和 TTX 不敏感型 Na 通道 (hNa1.5)。B. annulata 毒液的第二种作用是对 GABAAR 的激动作用，激活由 α1β2γ2、α3β2γ1 或 ρ1 同源受体组成的不同受体。由于 ELISA 测定法在毒液样本中检测到 GABA 的浓度在纳摩尔范围内，因此可以排除刺丝囊中的 GABA 直接激活 GABAAR。这表明 B. annulata 刺丝囊中的物质至少对哺乳动物离子通道产生了两种强烈且新颖的作用，这些作用对神经系统信号传导至关重要。
