Millar Ian D, Bruce Jason Ie, Brown Peter D
Faculty of Life Sciences, Core Technology Facility, University of Manchester, Manchester M13 9NT, UK.
Cerebrospinal Fluid Res. 2007 Sep 20;4:8. doi: 10.1186/1743-8454-4-8.
Knowledge of the diversity of ion channel form and function has increased enormously over the last 25 years. The initial impetus in channel discovery came with the introduction of the patch clamp method in 1981. Functional data from patch clamp experiments have subsequently been augmented by molecular studies which have determined channel structures. Thus the introduction of patch clamp methods to study ion channel expression in the choroid plexus represents an important step forward in our knowledge understanding of the process of CSF secretion.Two K+ conductances have been identified in the choroid plexus: Kv1 channel subunits mediate outward currents at depolarising potentials; Kir 7.1 carries an inward-rectifying conductance at hyperpolarising potentials. Both K+ channels are localised at the apical membrane where they may contribute to maintenance of the membrane potential while allowing the recycling of K+ pumped in by Na+-K+ ATPase. Two anion conductances have been identified in choroid plexus. Both have significant HCO3- permeability, and may play a role in CSF secretion. One conductance exhibits inward-rectification and is regulated by cyclic AMP. The other is carried by an outward-rectifying channel, which is activated by increases in cell volume. The molecular identity of the anion channels is not known, nor is it clear whether they are expressed in the apical or basolateral membrane. Recent molecular evidence indicates that choroid plexus also expresses the non-selective cation channels such as transient receptor potential channels (TRPV4 and TRPM3) and purinoceptor type 2 (P2X) receptor operated channels. In conclusion, good progress has been made in identifying the channels expressed in the choroid plexus, but determining the precise roles of these channels in CSF secretion remains a challenge for the future.
在过去25年里,人们对离子通道形式和功能多样性的认识有了极大的提高。通道发现的最初推动力来自1981年膜片钳技术的引入。随后,膜片钳实验的功能数据通过确定通道结构的分子研究得到了补充。因此,引入膜片钳方法来研究脉络丛中的离子通道表达代表了我们在脑脊液分泌过程知识理解上的重要一步。
Kv1通道亚基在去极化电位下介导外向电流;Kir 7.1在超极化电位下携带内向整流电导。两种钾离子通道都位于顶端膜,在那里它们可能有助于维持膜电位,同时允许由钠钾ATP酶泵入的钾离子循环利用。
在脉络丛中已鉴定出两种阴离子电导。两者都具有显著的碳酸氢根通透性,可能在脑脊液分泌中起作用。一种电导表现出内向整流,并受环磷酸腺苷调节。另一种由外向整流通道介导,该通道由细胞体积增加激活。阴离子通道的分子身份尚不清楚,它们是否在顶端膜或基底外侧膜表达也不清楚。最近的分子证据表明,脉络丛还表达非选择性阳离子通道,如瞬时受体电位通道(TRPV4和TRPM3)和嘌呤受体2型(P2X)受体操纵通道。
总之,在鉴定脉络丛中表达的通道方面已经取得了良好进展,但确定这些通道在脑脊液分泌中的精确作用仍然是未来的一个挑战。