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Advanced type 1 diabetes is associated with ASIC alterations in mouse lower thoracic dorsal root ganglia neurons

Domenii publicaţii > Ştiinţe medicale + Tipuri publicaţii > Articol în revistã ştiinţificã

Autori: Radu BM, Dumitrescu DI, Marin A, Banciu DD, Iancu AD, Selescu T, Radu M

Editorial: Cell Biochemistry and Biophysics, 68(1), p.9-23, 2014.

Rezumat:

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 wk 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 is inactivates faster, while ASIC2 slower; (ii) PcTx1 partly reverts diabetes effects against ASIC1- and ASIC2- inactivation. (iii) APETx2 maintains unaltered its 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 cause or the consequence of diabetic insensate neuropathy.

Cuvinte cheie: acid sensing ion channel, type 1 diabetes, thoracic dorsal root ganglia, channel abundance, channel biophysical characteristics

URL: http://link.springer.com/article/10.1007/s12013-013-9678-5