Cotero B V, Rebolledo-Antúnez S, Ortega-Blake I
Laboratorio de Cuernavaca, Instituto de Física, Universidad Nacional Autónoma de México, Apartado Postal 48-3, Cuernavaca, Morelos 62251, Mexico.
Biochim Biophys Acta. 1998 Oct 15;1375(1-2):43-51. doi: 10.1016/s0005-2736(98)00134-5.
Amphotericin B is an antimycotic agent that has been studied for a long time, both because of its pharmacological action and the interest in understanding how this ionic channel works. It has been proposed that the channel is formed by a barrel of monomers, and that the presence of sterol is needed for the formation of such a barrel. As a matter of fact this need of a sterol has been used as a guiding idea in attempts to design derivatives more efficient in the discrimination of the cholesterol containing membranes, as compared to the ergosterol containing ones, henceforth diminishing the unwanted side effects in its pharmacological use. In this work we show that unitary channels that appear in a cholesterol containing membrane also appear when this membrane is free of cholesterol. We prove this to be the case for two membranes, a biological one, asolectin, and a synthetic one, DMPC. We then advance the idea that the role of sterols in the formation of the amphotericin B channel is related to the effects they have on the structure of the membrane itself, rather than to a direct involvement in the channel formation. We further look into the effect that different cholesterol concentrations in the membrane produce on the single channel properties.
两性霉素B是一种已被研究很久的抗真菌剂，这既是因为其药理作用，也是因为人们对了解这种离子通道的工作原理感兴趣。有人提出，该通道由一桶单体形成，并且形成这样一桶需要固醇的存在。事实上，这种对固醇的需求已被用作一种指导思想，试图设计出比含麦角固醇的膜更能有效区分含胆固醇膜的衍生物，从而减少其药理使用中不必要的副作用。在这项工作中，我们表明，出现在含胆固醇膜中的单一通道，在该膜不含胆固醇时也会出现。我们证明两种膜都是这种情况，一种是生物膜，大豆卵磷脂，另一种是合成膜，二肉豆蔻酰磷脂酰胆碱。然后我们提出这样的观点，即固醇在两性霉素B通道形成中的作用与其对膜本身结构的影响有关，而不是直接参与通道形成。我们进一步研究了膜中不同胆固醇浓度对单通道特性的影响。
