Article

Different contributions of ASIC channels 1a, 2, and 3 in gastrointestinal mechanosensory function

Nerve Gut Research Laboratory, Hanson Institute, Department of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, Australia.
Gut (Impact Factor: 13.32). 11/2005; 54(10):1408-15. DOI: 10.1136/gut.2005.071084
Source: PubMed

ABSTRACT Members of the acid sensing ion channel (ASIC) family are strong candidates as mechanical transducers in sensory function. The authors have shown that ASIC1a has no role in skin but a clear influence in gastrointestinal mechanotransduction. Here they investigate further ASIC1a in gut mechanoreceptors, and compare its influence with ASIC2 and ASIC3.
Expression of ASIC1a, 2, and 3 mRNA was found in vagal (nodose) and dorsal root ganglia (DRG), and was lost in mice lacking the respective genes. Recordings of different classes of splanchnic colonic afferents and vagal gastro-oesophageal afferents revealed that disruption of ASIC1a increased the mechanical sensitivity of all afferents in both locations. Disruption of ASIC2 had varied effects: increased mechanosensitivity in gastro-oesophageal mucosal endings, decreases in gastro-oesophageal tension receptors, increases in colonic serosal endings, and no change in colonic mesenteric endings. In ASIC3-/- mice, all afferent classes had markedly reduced mechanosensitivity except gastro-oesophageal mucosal receptors. Observations of gastric emptying and faecal output confirmed that increases in mechanosensitivity translate to changes in digestive function in conscious animals.
These data show that ASIC3 makes a critical positive contribution to mechanosensitivity in three out of four classes of visceral afferents. The presence of ASIC1a appears to provide an inhibitory contribution to the ion channel complex, whereas the role of ASIC2 differs widely across subclasses of afferents. These findings contrast sharply with the effects of ASIC1, 2, and 3 in skin, suggesting that targeting these subunits with pharmacological agents may have different and more pronounced effects on mechanosensitivity in the viscera.

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    • "The acid-sensing ion channels (ASICs) are proton-gated trimeric channels (Gonzales et al., 2009; Jasti et al., 2007) that belong to the degenerin/epithelial sodium channel (DEG/ENaC) family (Kellenberger and Schild, 2002) and are implicated in ischemia (Gao et al., 2005; Sutherland et al., 2001; Xiong et al., 2004; Yagi et al., 2006), neurotransmission (Wemmie et al., 2002), epilepsy (Ziemann et al., 2008), mechanosensation (Lu et al., 2009; Page et al., 2005; Price et al., 2000, 2001), chemosensation (Ziemann et al., 2009), and pain perception (Chen et al., 2002; Deval et al., 2008; Duan et al., 2007; Mazzuca et al., 2007; Sluka et al., 2003; Xu and Duan, 2009). As their name indicates , ASICs are activated by extracellular acidosis (Krishtal, 2003; Waldmann et al., 1997; Wemmie et al., 2006). "
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