Iron, an essential element for most living organism, participates in a wide variety of physiological processes. Disturbance in iron homeostasis has been associated with numerous pathologies, particularly in the heart and brain, which are the most susceptible organs. Under iron-overload conditions, the generation of reactive oxygen species leads to impairment in Ca²⁺ signaling, fundamentally implicated in cardiac and neuronal physiology. Since iron excess is accompanied by increased expression of iron-storage protein, ferritin, we examined whether ferritin has an effect on the ryanodine receptor - isoform 2 (RYR2), which is one of the major components of Ca²⁺ signaling. Using the method of planar lipid membranes, we show that ferritin induced an abrupt, permanent blockage of the RYR2 channel. The ferritin effect was strongly voltage dependent and competitively antagonized by cytosolic TEA+, an impermeant RYR2 blocker. Our results collectively indicate that monomeric ferritin highly likely blocks the RYR2 channel by a direct electrostatic interaction within the wider region of the channel permeation pathway.

铁是大多数生物体的必需元素，参与多种生理过程。铁稳态的紊乱与许多病理有关，特别是在心脏和大脑中，它们是最易感的器官。在铁过载条件下，活性氧的产生导致 Ca ²⁺信号传导受损，从根本上与心脏和神经元生理有关。由于铁过量伴随着铁储存蛋白铁蛋白的表达增加，我们检查了铁蛋白是否对兰尼碱受体同工型 2 (RYR2) 有影响，后者是 Ca ²⁺的主要成分之一信号。使用平面脂质膜的方法，我们表明铁蛋白诱导了 RYR2 通道的突然、永久性阻塞。铁蛋白效应强烈依赖于电压，并被胞质 TEA+（一种不可渗透的 RYR2 阻滞剂）竞争性拮抗。我们的结果共同表明，单体铁蛋白很可能通过通道渗透途径更广泛区域内的直接静电相互作用来阻断 RYR2 通道。