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Upregulation of T-type Ca(2+) channels in long-term diabetes determines increased excitability of a specific type of capsaicin-insensitive DRG neurons
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 Ca(2+) current. In longer–term diabetes (after the 8th week) therm...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490764/ https://www.ncbi.nlm.nih.gov/pubmed/25986602 http://dx.doi.org/10.1186/s12990-015-0028-z |
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author | Duzhyy, Dmytro E Viatchenko-Karpinski, Viacheslav Y Khomula, Eugen V Voitenko, Nana V Belan, Pavel V |
author_facet | Duzhyy, Dmytro E Viatchenko-Karpinski, Viacheslav Y Khomula, Eugen V Voitenko, Nana V Belan, Pavel V |
author_sort | Duzhyy, Dmytro E |
collection | PubMed |
description | 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 Ca(2+) 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 Ca(2+) 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 Ni(2+) (50 μM) implicates prevalence of Ca(v)3.2 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(v)3.2 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. |
format | Online Article Text |
id | pubmed-4490764 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44907642015-07-04 Upregulation of T-type Ca(2+) channels in long-term diabetes determines increased excitability of a specific type of capsaicin-insensitive DRG neurons Duzhyy, Dmytro E Viatchenko-Karpinski, Viacheslav Y Khomula, Eugen V Voitenko, Nana V Belan, Pavel V Mol Pain Research 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 Ca(2+) 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 Ca(2+) 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 Ni(2+) (50 μM) implicates prevalence of Ca(v)3.2 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(v)3.2 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. BioMed Central 2015-05-20 /pmc/articles/PMC4490764/ /pubmed/25986602 http://dx.doi.org/10.1186/s12990-015-0028-z Text en © Duzhyy et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Duzhyy, Dmytro E Viatchenko-Karpinski, Viacheslav Y Khomula, Eugen V Voitenko, Nana V Belan, Pavel V Upregulation of T-type Ca(2+) channels in long-term diabetes determines increased excitability of a specific type of capsaicin-insensitive DRG neurons |
title | Upregulation of T-type Ca(2+) channels in long-term diabetes determines increased excitability of a specific type of capsaicin-insensitive DRG neurons |
title_full | Upregulation of T-type Ca(2+) channels in long-term diabetes determines increased excitability of a specific type of capsaicin-insensitive DRG neurons |
title_fullStr | Upregulation of T-type Ca(2+) channels in long-term diabetes determines increased excitability of a specific type of capsaicin-insensitive DRG neurons |
title_full_unstemmed | Upregulation of T-type Ca(2+) channels in long-term diabetes determines increased excitability of a specific type of capsaicin-insensitive DRG neurons |
title_short | Upregulation of T-type Ca(2+) channels in long-term diabetes determines increased excitability of a specific type of capsaicin-insensitive DRG neurons |
title_sort | upregulation of t-type ca(2+) channels in long-term diabetes determines increased excitability of a specific type of capsaicin-insensitive drg neurons |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490764/ https://www.ncbi.nlm.nih.gov/pubmed/25986602 http://dx.doi.org/10.1186/s12990-015-0028-z |
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