Hu Jing, Lewin Gary R
Max-Delbrück Center for Molecular Medicine and Charité Universitätsmedizin Berlin, Robert-Rössle-Strasse 10, Berlin-Buch D-13125, Germany.
J Physiol. 2006 Dec 15;577(Pt 3):815-28. doi: 10.1113/jphysiol.2006.117648. Epub 2006 Oct 12.
Almost all sensory neurones in the dorsal root ganglia have a mechanosensory function. The transduction of mechanical stimuli in vivo takes place exclusively at the sensory ending. For cutaneous sensory receptors it has so far proved impossible to directly record the mechanically gated receptor potential because of the small size and inaccessibility of the sensory ending. Here we investigate whether mechanosensitive currents are present in the neurites of freshly isolated adult mouse sensory neurones in culture. Almost all sensory neurone neurites possess currents gated by submicrometre displacement stimuli (92%). Three types of mechanically activated conductance were characterized based on different inactivation kinetics. A rapidly adapting conductance was found in larger sensory neurones with narrow action potentials characteristic of mechanoreceptors. Slowly and intermediate adapting conductances were found exclusively in putative nociceptive neurones. Mechanically activated currents with similar kinetics were found also after stimulating the cell soma. However, soma currents were only observed in around 60% of cells tested and the displacement threshold was several times larger than for the neurite (approximately 6 microm). The reversal potential of the rapidly adapting current indicated that this current is largely selective for sodium ions whereas the slowly adapting current is non-selective. It is likely that distinct ion channel entities underlie these two currents. In summary, our data suggest that the high sensitivity and robustness of mechanically gated currents in the sensory neurite make this a useful in vitro model for the mechanosensitive sensory endings in vivo.
几乎所有背根神经节中的感觉神经元都具有机械感觉功能。体内机械刺激的转导仅在感觉末梢发生。对于皮肤感觉感受器,由于感觉末梢体积小且难以接近,迄今为止,直接记录机械门控受体电位已被证明是不可能的。在这里,我们研究了在培养的新鲜分离的成年小鼠感觉神经元的神经突中是否存在机械敏感电流。几乎所有感觉神经元的神经突都具有由亚微米级位移刺激门控的电流(92%)。基于不同的失活动力学,对三种类型的机械激活电导进行了表征。在具有机械感受器特征性窄动作电位的较大感觉神经元中发现了一种快速适应电导。缓慢适应和中等适应电导仅在假定的伤害性神经元中发现。在刺激细胞体后也发现了具有相似动力学的机械激活电流。然而,仅在约60%的测试细胞中观察到体细胞电流,并且位移阈值比神经突的位移阈值大几倍(约6微米)。快速适应电流的反转电位表明,该电流在很大程度上对钠离子具有选择性,而缓慢适应电流是非选择性的。这两种电流可能由不同的离子通道实体构成。总之,我们的数据表明,感觉神经突中机械门控电流的高敏感性和稳健性使其成为体内机械敏感感觉末梢的有用体外模型。