title: Advanced type 1 diabetes is associated with ASIC alterations in mouse lower thoracic dorsal root ganglia neurons.
abstract: 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.
authors.affiliation: Section of Anatomy and Histology, Department of Neurological, Neuropsychological, Morphological and Movement Sciences, University of Verona, Strada Le Grazie 8, 37134, Verona, Italy.
authors.forename: Beatrice Mihaela
authors.initials: BM
authors.lastname: Radu
authors.forename: Diana Ionela
authors.initials: DI
authors.lastname: Dumitrescu
authors.forename: Adela
authors.initials: A
authors.lastname: Marin
authors.forename: Daniel Dumitru
authors.initials: DD
authors.lastname: Banciu
authors.forename: Adina Daniela
authors.initials: AD
authors.lastname: Iancu
authors.forename: Tudor
authors.initials: T
authors.lastname: Selescu
authors.forename: Mihai
authors.initials: M
authors.lastname: Radu
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003064:Cnidarian Venoms / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology*; D005838:Genotype; D007328:Insulin / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013111:Spider Venoms / Q000494:pharmacology
chemical_list: C501880:APETx2 protein, Anthopleura elegantissima; C568267:ASIC1 protein, mouse; C568265:ASIC2 protein, mouse; C508378:ASIC3 protein, mouse; D062565:Acid Sensing Ion Channels; D003064:Cnidarian Venoms; D007328:Insulin; C413209:PcTX1 protein, Psalmopoeus cambridgei; D010455:Peptides; D012333:RNA, Messenger; D013111:Spider Venoms