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

被引:221
作者
Page, AJ
Brierley, SM
Martin, CM
Price, MP
Symonds, E
Butler, R
Wemmie, JA
Blackshaw, LA
机构
[1] Royal Adelaide Hosp, Dept Gastroenterol Hepatol & Gen Med, Hanson Inst, Nerve Gut Res Lab, Adelaide, SA 5000, Australia
[2] Univ Adelaide, Discipline Physiol, Adelaide, SA, Australia
[3] Univ Adelaide, Dept Med, Adelaide, SA 5001, Australia
[4] Dept Vet Affairs Med Ctr, Dept Psychiat, Iowa City, IA USA
[5] Univ Iowa, Coll Med, Dept Physiol & Biophys, Iowa City, IA 52242 USA
[6] Univ Iowa, Coll Med, Howard Hughes Inst, Iowa City, IA 52242 USA
[7] Womens & Childrens Hosp, Ctr Paediat & Adolescent Gastroenterol, Adelaide, SA, Australia
关键词
D O I
10.1136/gut.2005.071084
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Aims: 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. Methods and results: 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. Conclusions: 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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页码:1408 / 1415
页数:8
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