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- W1979155572 endingPage "649" @default.
- W1979155572 startingPage "636" @default.
- W1979155572 abstract "Streptozotocin (STZ)-induced type 1 diabetes in rats leads to the development of peripheral diabetic neuropathy (PDN) manifested as thermal hyperalgesia at early stages (4th week) followed by hypoalgesia after 8weeks of diabetes development. Here we found that 6-7 week STZ-diabetic rats developed either thermal hyper- (18%), hypo- (25%) or normalgesic (57%) types of PDN. These developmentally similar diabetic rats were studied in order to analyze mechanisms potentially underlying different thermal nociception. The proportion of IB4-positive capsaicin-sensitive small DRG neurons, strongly involved in thermal nociception, was not altered under different types of PDN implying differential changes at cellular and molecular level. We further focused on properties of T-type calcium and TRPV1 channels, which are known to be involved in Ca(2+) signaling and pathological nociception. Indeed, TRPV1-mediated signaling in these neurons was downregulated under hypo- and normalgesia and upregulated under hyperalgesia. A complex interplay between diabetes-induced changes in functional expression of Cav3.2 T-type calcium channels and depolarizing shift of their steady-state inactivation resulted in upregulation of these channels under hyper- and normalgesia and their downregulation under hypoalgesia. As a result, T-type window current was increased by several times under hyperalgesia partially underlying the increased resting [Ca(2+)]i observed in the hyperalgesic rats. At the same time Cav3.2-dependent Ca(2+) signaling was upregulated in all types of PDN. These findings indicate that alterations in functioning of Cav3.2 T-type and TRPV1 channels, specific for each type of PDN, may underlie the variety of pain syndromes induced by type 1 diabetes." @default.
- W1979155572 created "2016-06-24" @default.
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- W1979155572 creator A5063833463 @default.
- W1979155572 creator A5083522302 @default.
- W1979155572 creator A5087556050 @default.
- W1979155572 date "2013-05-01" @default.
- W1979155572 modified "2023-10-14" @default.
- W1979155572 title "Specific functioning of Cav3.2 T-type calcium and TRPV1 channels under different types of STZ-diabetic neuropathy" @default.
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- W1979155572 doi "https://doi.org/10.1016/j.bbadis.2013.01.017" @default.
- W1979155572 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23376589" @default.
- W1979155572 hasPublicationYear "2013" @default.
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