Khalsa P S, Ge W, Uddin M Zia, Hadjiargyrou M
Department of Biomedical Engineering, State University of New York, HSC T18-031, Stony Brook, NY 11794-8181, USA.
Neuroscience. 2004;129(2):447-59. doi: 10.1016/j.neuroscience.2004.08.011.
The role of a transmembrane protein, integrin alpha2beta1, to modulate the neural responses of cutaneous mechanoreceptors to mechanical indentation was examined using an isolated skin-nerve preparation in a rat model. Skin and its intact innervation were harvested from the medial thigh of the hindlimb and placed in a dish containing synthetic interstitial fluid. Using a standard teased nerve preparation, the neural responses of single slowly or rapidly adapting mechanoreceptors (SA or RA, respectively) were identified and the afferents categorized according to standard protocols (i.e. response to constant stimuli). The most sensitive spot of a mechanoreceptor's receptive field was identified and then stimulated using controlled compressive stress (constant or dynamic loads between threshold and saturation load for SAs and RAs, respectively). Loads were applied before, during, and after passive diffusion into the skin of a function-blocking anti-integrin alpha2 monoclonal antibody (FBmAb) or one of two types of control antibodies (immunoglobulin G or a FBmAb conjugated with a secondary antibody). The sensitivities of both SA and RA mechanoreceptors were profoundly reduced in the presence of the FBmAb, while not changing the waveforms of their action potentials or their adaptation properties. Both control antibodies had no significant effect on mechanoreceptors' sensitivities. Following removal of the FBmAb, the effects in some neurons were partially reversible. Taken together, the data from this study support the hypothesis that integrin alpha2beta1 plays a significant role in modulating mechanoreceptive response to compressive indentation.
在大鼠模型中，使用离体皮肤 - 神经标本，研究了跨膜蛋白整合素α2β1在调节皮肤机械感受器对机械压痕的神经反应中的作用。从后肢内侧大腿采集皮肤及其完整的神经支配，置于含有合成组织液的培养皿中。使用标准的神经分离标本，识别单个慢适应或快适应机械感受器（分别为SA或RA）的神经反应，并根据标准方案（即对恒定刺激的反应）对传入神经进行分类。确定机械感受器感受野中最敏感的部位，然后分别使用可控的压缩应力（SA和RA分别为阈值和饱和负荷之间的恒定或动态负荷）进行刺激。在向皮肤被动扩散功能阻断性抗整合素α2单克隆抗体（FBmAb）或两种对照抗体之一（免疫球蛋白G或与二抗偶联的FBmAb）之前、期间和之后施加负荷。在存在FBmAb的情况下，SA和RA机械感受器的敏感性均显著降低，而其动作电位的波形或适应特性未发生改变。两种对照抗体对机械感受器的敏感性均无显著影响。去除FBmAb后，某些神经元中的效应部分可逆。综上所述，本研究的数据支持以下假设：整合素α2β1在调节对压缩压痕的机械感受反应中起重要作用。
