Differential Localization of Acid-Sensing Ion Channels 1 and 2 in Human Cutaneus Pacinian Corpuscles

Calavia, M.G.; Montano, J.A; García‐Suárez, Olivia; Feito, Jorge; Guervós, Marta Alonso; Germanà, Antonino; Soto, Miguel; Pérez-Piñera, Pablo; Cobo, Juan; Vega, J.A.

doi:10.1007/s10571-010-9511-2

Cited by 39 publications

(37 citation statements)

References 37 publications

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“…It would be also interesting for future studies to investigate mechanically activated current in dissociate DRG neurons to characterize other mechanosensory phenotypes of ASIC TKO s. We have shown slower mean conduction velocity (CV) of Aδ-AMs from ASIC TKOs. Previous studies have demonstrated the expression of ASIC2 or other channels from DEG/ENaC superfamily by human or rat Schwann cells [56], [57]. Therefore, while the exact underlying mechanism remains unclear, warranting further investigation, this might suggest a possible role of ASIC s in Schwann cell function and axonal conduction in sub-populations of afferents.…”

Section: Discussionmentioning

confidence: 97%

Simultaneous Disruption of Mouse ASIC1a, ASIC2 and ASIC3 Genes Enhances Cutaneous Mechanosensitivity

et al. 2012

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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.

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Section: Discussionmentioning

confidence: 97%

Simultaneous Disruption of Mouse ASIC1a, ASIC2 and ASIC3 Genes Enhances Cutaneous Mechanosensitivity

et al. 2012

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“…2F). Likewise, the ASIC-1, MEC-10, and MEC-6 proteins have clear orthologs in insects and in higher animals, including humans (SNN1G, PON1, and ACCN2), that form a mechanosensitive complex in branched subcutaneous sensory neurons (although PON1 may be secreted) (14,(32)(33)(34). Thus, our findings suggest the possibly of a conserved humidity-sensing strategy in which humidity levels may be encoded by the extent to which the dendritic field is stretched by skin hydration.…”

Section: Discussionmentioning

confidence: 99%

Humidity sensation requires both mechanosensory and thermosensory pathways in Caenorhabditis elegans

Russell

Vidal-Gadea

Makay

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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All terrestrial animals must find a proper level of moisture to ensure their health and survival. The cellular-molecular basis for sensing humidity is unknown in most animals, however. We used the model nematode Caenorhabditis elegans to uncover a mechanism for sensing humidity. We found that whereas C. elegans showed no obvious preference for humidity levels under standard culture conditions, worms displayed a strong preference after pairing starvation with different humidity levels, orienting to gradients as shallow as 0.03% relative humidity per millimeter. Cell-specific ablation and rescue experiments demonstrate that orientation to humidity in C. elegans requires the obligatory combination of distinct mechanosensitive and thermosensitive pathways. The mechanosensitive pathway requires a conserved DEG/ENaC/ ASIC mechanoreceptor complex in the FLP neuron pair. Because humidity levels influence the hydration of the worm's cuticle, our results suggest that FLP may convey humidity information by reporting the degree that subcuticular dendritic sensory branches of FLP neurons are stretched by hydration. The thermosensitive pathway requires cGMP-gated channels in the AFD neuron pair. Because humidity levels affect evaporative cooling, AFD may convey humidity information by reporting thermal flux. Thus, humidity sensation arises as a metamodality in C. elegans that requires the integration of parallel mechanosensory and thermosensory pathways. This hygrosensation strategy, first proposed by Thunberg more than 100 y ago, may be conserved because the underlying pathways have cellular and molecular equivalents across a wide range of species, including insects and humans. mechanosensation | thermosensation M oisture is essential for life. As such, many animals have adapted different behavioral mechanisms to migrate toward their preferred moisture level (hygrotaxis) (1-6). For instance, Drosophila avoid high humidity that impedes flight, whereas green frogs orient toward high humidity to maintain hydration (5, 6). Animals also sense moisture levels to determine important information about their environment; for example, moths detect humidity levels around flowers to deduce which ones might be damaged and contain less nectar (7). These behaviors are often critical to keep an animal within its niche and regulate essential processes such as growth and reproduction. Thus, it is surprising that the molecular basis for how different humidity levels are detected and encoded by the nervous system (hygrosensation) remains unknown in most animals.The search for humidity receptors has achieved the most progress in insects. For instance, distinct sets of hygrosensitive neurons have been found in dome-shaped organs on the antenna of the giant cockroach (8). One set activates with moist air, and the other set responds to dry air. Similar moist and dry receptive neurons have been detected in the branched arista subsegment of the antennae in adult Drosophila (9). Removal of the arista or deletion of any one of three TRP channels expres...

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“…For instance, ASIC1a and ASIC3 are the most sensitive to H + channel proteins of these subunits than other ASIC members, which are activated by pH levels below 7.0 [33]. In contrast to ASIC1a homomers, ASIC2a shows low sensitivity to reduced extracellular pH (pH50=4.35) and slow channel inactivation [34,35]. Moreover, homomeric ASIC2a displays slower kinetics of desensitization than ASIC1a homomers [36,37].…”

Section: Structure and Characteristics Of Asicsmentioning

confidence: 99%

Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative Diseases

Zhou

Wang³

et al. 2016

Aging and disease

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Differential Localization of Acid-Sensing Ion Channels 1 and 2 in Human Cutaneus Pacinian Corpuscles

Cited by 39 publications

References 37 publications

Simultaneous Disruption of Mouse ASIC1a, ASIC2 and ASIC3 Genes Enhances Cutaneous Mechanosensitivity

Simultaneous Disruption of Mouse ASIC1a, ASIC2 and ASIC3 Genes Enhances Cutaneous Mechanosensitivity

Humidity sensation requires both mechanosensory and thermosensory pathways in Caenorhabditis elegans

Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative Diseases

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