Advanced Type 1 Diabetes is Associated with ASIC Alterations in Mouse Lower Thoracic Dorsal Root Ganglia Neurons
| Autor: | Tudor Selescu, Diana Ionela Dumitrescu, Adina Daniela Iancu, Daniel Dumitru Banciu, Adela Marin, Mihai Radu, Beatrice Mihaela Radu |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Patch-Clamp Techniques Genotype type 1 diabetes Biophysics Ischemia acid-sensing ion channel Spider Venoms Mice Transgenic Inflammation Immunofluorescence Biochemistry Mice Cnidarian Venoms Ganglia Spinal Internal medicine Diabetes mellitus thoracic dorsal root ganglia medicine Animals Insulin RNA Messenger Cells Cultured Acid-sensing ion channel Ion channel Neurons Mice Inbred BALB C Messenger RNA Hypoalgesia medicine.diagnostic_test Chemistry Cell Biology General Medicine Anatomy medicine.disease channel abundance Acid Sensing Ion Channels channel biophysical characteristics Diabetes Mellitus Type 1 Endocrinology medicine.symptom Peptides |
| Zdroj: | Cell Biochemistry and Biophysics. 68:9-23 |
| ISSN: | 1559-0283 1085-9195 |
| DOI: | 10.1007/s12013-013-9678-5 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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