Section of Anatomy and Histology, Department of Neurological, Neuropsychological, Morphological and Movement Sciences, University of Verona, Strada Le Grazie 8, 37134, Verona, Italy.
Cell Biochem Biophys. 2014 Jan;68(1):9-23. doi: 10.1007/s12013-013-9678-5.
Acid-sensing ion channels (ASICs) from dorsal root ganglia (DRG) neurons are proton sensors during ischemia and inflammation. Little is known about their role in type 1 diabetes (T1D). Our study was focused on ASICs alterations determined by advanced T1D status. Primary neuronal cultures were obtained from lower (T9-T12) thoracic DRG neurons from Balb/c and TCR-HA(+/-)/Ins-HA(+/-) diabetic male mice (16 weeks of age). Patch-clamp recordings indicate a change in the number of small DRG neurons presenting different ASIC-type currents. Multiple molecular sites of ASICs are distinctly affected in T1D, probably due to particular steric constraints for glycans accessibility to the active site: (i) ASIC1 current inactivates faster, while ASIC2 is slower; (ii) PcTx1 partly reverts diabetes effects against ASIC1- and ASIC2-inactivations; (iii) APETx2 maintains unaltered potency against ASIC3 current amplitude, but slows ASIC3 inactivation. Immunofluorescence indicates opposite regulation of different ASIC transcripts while qRT-PCR shows that ASIC mRNA ranking (ASIC2 > ASIC1 > ASIC3) remains unaltered. In conclusion, our study has identified biochemical and biophysical ASIC changes in lower thoracic DRG neurons due to advanced T1D. As hypoalgesia is present in advanced T1D, ASICs alterations might be the cause or the consequence of diabetic insensate neuropathy.
酸感应离子通道（ASICs）来源于背根神经节（DRG）神经元，在缺血和炎症期间是质子传感器。然而，关于它们在 1 型糖尿病（T1D）中的作用知之甚少。我们的研究重点是由先进的 T1D 状态决定的 ASICs 改变。从 16 周龄 Balb/c 和 TCR-HA(+/-)/Ins-HA(+/-)糖尿病雄性小鼠的下胸（T9-T12）DRG 神经元中获得原代神经元培养物。膜片钳记录表明，呈现不同 ASIC 型电流的小 DRG 神经元数量发生变化。T1D 明显影响 ASICs 的多个分子部位，可能是由于糖链对活性部位的空间位阻的特殊限制：（i）ASIC1 电流失活更快，而 ASIC2 较慢；（ii）PcTx1 部分逆转糖尿病对 ASIC1 和 ASIC2 失活的影响；（iii）APETx2 保持对 ASIC3 电流幅度的不变效力，但减慢 ASIC3 失活。免疫荧光表明不同 ASIC 转录本的相反调节，而 qRT-PCR 表明 ASIC mRNA 排名（ASIC2>ASIC1>ASIC3）保持不变。总之，我们的研究已经确定了由于先进的 T1D，下胸 DRG 神经元中的生物化学和生物物理 ASIC 变化。由于在先进的 T1D 中存在低痛觉，ASICs 的改变可能是糖尿病感觉神经病变的原因或后果。
