Department of Anesthesia, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
PLoS One. 2012;7(4):e35225. doi: 10.1371/journal.pone.0035225. Epub 2012 Apr 10.
Three observations have suggested that acid-sensing ion channels (ASICs) might be mammalian cutaneous mechanoreceptors; they are structurally related to Caenorhabditis elegans mechanoreceptors, they are localized in specialized cutaneous mechanosensory structures, and mechanical displacement generates an ASIC-dependent depolarization in some neurons. However, previous studies of mice bearing a single disrupted ASIC gene showed only subtle or no alterations in cutaneous mechanosensitivity. Because functional redundancy of ASIC subunits might explain limited phenotypic alterations, we hypothesized that disrupting multiple ASIC genes would markedly impair cutaneous mechanosensation. We found the opposite. In behavioral studies, mice with simultaneous disruptions of ASIC1a, -2 and -3 genes (triple-knockouts, TKOs) showed increased paw withdrawal frequencies when mechanically stimulated with von Frey filaments. Moreover, in single-fiber nerve recordings of cutaneous afferents, mechanical stimulation generated enhanced activity in A-mechanonociceptors of ASIC TKOs compared to wild-type mice. Responses of all other fiber types did not differ between the two genotypes. These data indicate that ASIC subunits influence cutaneous mechanosensitivity. However, it is unlikely that ASICs directly transduce mechanical stimuli. We speculate that physical and/or functional association of ASICs with other components of the mechanosensory transduction apparatus contributes to normal cutaneous mechanosensation.
有三个观察结果表明，酸敏离子通道（ASICs）可能是哺乳动物的皮肤机械感受器；它们在结构上与秀丽隐杆线虫的机械感受器相关，定位于专门的皮肤机械感觉结构中，并且机械位移在一些神经元中产生依赖 ASIC 的去极化。然而，先前对携带单个 ASIC 基因破坏的小鼠的研究表明，皮肤机械敏感性只有细微或没有改变。因为 ASIC 亚基的功能冗余可能解释了有限的表型改变，我们假设破坏多个 ASIC 基因将显著损害皮肤机械感觉。我们发现了相反的结果。在行为研究中，ASIC1a、-2 和 -3 基因同时破坏的小鼠（三重敲除小鼠，TKOs）在用冯弗雷丝纤维机械刺激时表现出更高的爪缩回频率。此外，在皮肤传入神经的单纤维神经记录中，与野生型小鼠相比，ASIC TKOs 的 A 型机械伤害感受器的机械刺激产生了增强的活性。两种基因型之间所有其他纤维类型的反应没有差异。这些数据表明，ASIC 亚基影响皮肤机械敏感性。然而，ASIC 不太可能直接转导机械刺激。我们推测，ASICs 与机械感觉转导装置的其他组成部分的物理和/或功能关联有助于正常的皮肤机械感觉。
