Siskind Leah J, Davoody Amirparviz, Lewin Naomi, Marshall Stephanie, Colombini Marco
Department of Biology, University of Maryland, College Park, Maryland 20742 USA.
Biophys J. 2003 Sep;85(3):1560-75. doi: 10.1016/S0006-3495(03)74588-3.
Ceramides are known to play a major regulatory role in apoptosis by inducing cytochrome c release from mitochondria. We have previously reported that ceramide, but not dihydroceramide, forms large and stable channels in phospholipid membranes and outer membranes of isolated mitochondria. C(2)-ceramide channel formation is characterized by conductance increments ranging from <1 to >200 nS. These conductance increments often represent the enlargement and contracture of channels rather than the opening and closure of independent channels. Enlargement is supported by the observation that many small conductance increments can lead to a large decrement. Also the initial conductances favor cations, but this selectivity drops dramatically with increasing total conductance. La(+3) causes rapid ceramide channel disassembly in a manner indicative of large conducting structures. These channels have a propensity to contract by a defined size (often multiples of 4 nS) indicating the formation of cylindrical channels with preferred diameters rather than a continuum of sizes. The results are consistent with ceramides forming barrel-stave channels whose size can change by loss or insertion of multiple ceramide columns.
已知神经酰胺通过诱导细胞色素c从线粒体释放，在细胞凋亡中发挥主要调节作用。我们之前报道过，神经酰胺而非二氢神经酰胺，能在磷脂膜和分离线粒体的外膜中形成大且稳定的通道。C(2)-神经酰胺通道形成的特征是电导增量范围从<1到>200 nS。这些电导增量通常代表通道的扩大和收缩，而非独立通道的开放和关闭。许多小电导增量可导致大幅减小这一观察结果支持了通道扩大的观点。而且初始电导有利于阳离子，但随着总电导增加，这种选择性会急剧下降。La(+3)以一种表明大导电结构的方式导致神经酰胺通道迅速解体。这些通道倾向于按确定大小收缩（通常是4 nS的倍数），这表明形成了具有优选直径的圆柱形通道，而非连续变化的大小。结果与神经酰胺形成桶板通道一致，其大小可通过多个神经酰胺柱的丢失或插入而改变。
