Upregulation of T-type Ca2+ channels in long-term diabetes determines increased excitability of a specific type of capsaicin-insensitive DRG neurons

Molecular Pain

Pavel V Belan²  Nana V Voitenko²  Eugen V Khomula¹  Viacheslav Y Viatchenko-Karpinski²  Dmytro E Duzhyy² 

[1] International Center of Molecular Physiology of National Academy of Science of Ukraine, 4 Bogomoletz street, Kyiv, 01024, Ukraine;Department of General Physiology of the CNS and State Key Laboratory of Molecular and Cellular Biology, Bogomoletz Institute of Physiology of National Academy of Science of Ukraine, 4 Bogomoletz street, Kyiv, 01024, Ukraine

关键词: Capsaicin-insensitive;    Excitability;    DRG neurons;    T-type calcium channels;    Pain;    Diabetes;   

Others  :  1208581
DOI  :  10.1186/s12990-015-0028-z

 received in 2015-01-16, accepted in 2015-05-13,  发布年份 2015

【 摘 要 】

Background

Previous studies have shown that increased excitability of capsaicin-sensitive DRG neurons and thermal hyperalgesia in rats with short-term (2–4 weeks) streptozotocin-induced diabetes is mediated by upregulation of T-type Ca²⁺ current. In longer–term diabetes (after the 8th week) thermal hyperalgesia is changed to hypoalgesia that is accompanied by downregulation of T-type current in capsaicin-sensitive small-sized nociceptors. At the same time pain symptoms of diabetic neuropathy other than thermal persist in STZ-diabetic animals and patients during progression of diabetes into later stages suggesting that other types of DRG neurons may be sensitized and contribute to pain. In this study, we examined functional expression of T-type Ca²⁺ channels in capsaicin-insensitive DRG neurons and excitability of these neurons in longer-term diabetic rats and in thermally hypoalgesic diabetic rats.

Results

Here we have demonstrated that in STZ-diabetes T-type current was upregulated in capsaicin-insensitive low-pH-sensitive small-sized nociceptive DRG neurons of longer-term diabetic rats and thermally hypoalgesic diabetic rats. This upregulation was not accompanied by significant changes in biophysical properties of T-type channels suggesting that a density of functionally active channels was increased. Sensitivity of T-type current to amiloride (1 mM) and low concentration of Ni²⁺ (50 μM) implicates prevalence of Ca_v3.2 subtype of T-type channels in the capsaicin-insensitive low-pH-sensitive neurons of both naïve and diabetic rats. The upregulation of T-type channels resulted in the increased neuronal excitability of these nociceptive neurons revealed by a lower threshold for action potential initiation, prominent afterdepolarizing potentials and burst firing. Sodium current was not significantly changed in these neurons during long-term diabetes and could not contribute to the diabetes-induced increase of neuronal excitability.

Conclusions

Capsaicin-insensitive low-pH-sensitive type of DRG neurons shows diabetes-induced upregulation of Ca_v3.2 subtype of T-type channels. This upregulation results in the increased excitability of these neurons and may contribute to nonthermal nociception at a later-stage diabetes.

【 授权许可】

   
2015 Duzhyy et al.; licensee BioMed Central.

【 图 表 】

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