Opiate-mediated inhibition of calcium signaling is decreased in dorsal root ganglion neurons from the diabetic BB/W rat.

Hall, Karen E.; Sima, Anders A. F.; Wiley, John W.

doi:10.1172/jci118530

Cited by 41 publications

(41 citation statements)

References 45 publications

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“…and Ca V 1.3 -/-b cells. This is in line with previous findings from our group and others [19,[42][43][44][45]. More importantly, we are able to mechanistically interpret T1D serum-induced hyperactivation of b cell Ca V 1 channels by thoroughly examining the biophysical properties of single Ca V 1 channels in Ca V 1.…”

Section: Discussionsupporting

confidence: 91%

CaV1.2 and CaV1.3 channel hyperactivation in mouse islet β cells exposed to type 1 diabetic serum

Yang

Shi

et al. 2014

Cell. Mol. Life Sci.

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The voltage-gated Ca(2+) (CaV) channel acts as a key player in β cell physiology and pathophysiology. β cell CaV channels undergo hyperactivation subsequent to exposure to type 1 diabetic (T1D) serum resulting in increased cytosolic free Ca(2+) concentration and thereby Ca(2+)-triggered β cell apoptosis. The present study was aimed at revealing the subtypes of CaV1 channels hyperactivated by T1D serum as well as the biophysical mechanisms responsible for T1D serum-induced hyperactivation of β cell CaV1 channels. Patch-clamp recordings and single-cell RT-PCR analysis were performed in pancreatic β cells from CaV1 channel knockout and corresponding control mice. We now show that functional CaV1.3 channels are expressed in a subgroup of islet β cells from CaV1.2 knockout mice (CaV1.2(-/-)). T1D serum enhanced whole-cell CaV currents in islet β cells from CaV1.3 knockout mice (CaV1.3(-/-)). T1D serum increased the open probability and number of functional unitary CaV1 channels in CaV1.2(-/-) and CaV1.3(-/-) β cells. These data demonstrate that T1D serum hyperactivates both CaV1.2 and CaV1.3 channels by increasing their conductivity and number. These findings suggest CaV1.2 and CaV1.3 channels as potential targets for anti-diabetes therapy.

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Section: Discussionsupporting

confidence: 91%

CaV1.2 and CaV1.3 channel hyperactivation in mouse islet β cells exposed to type 1 diabetic serum

Yang

Shi

et al. 2014

Cell. Mol. Life Sci.

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“…Aside from the latter point, many researchers have noticed the presence of mechanical hyperalgesia in STZ-induced diabetic animals. In fact, high glucose per se (26), changes of neurotransmitters (27), alterations of opioid metabolism and receptors (28,29), or physiologically increased responsiveness or abnormalities of ion channels of neurons (15,18,30,31,32) have been proposed as contributing factors to hyperalgesia. Many reports have supported the significant effect of PKC modulators on the generation of pain; PKC may contribute to primary afferent C-fiber excitability, because phorbol esters can depolarize cultured DRG neurons with C-fiber properties (33).…”

Section: Discussionmentioning

confidence: 99%

Protein Kinase Cβ Selective Inhibitor LY333531 Attenuates Diabetic Hyperalgesia Through Ameliorating cGMP Level of Dorsal Root Ganglion Neurons

et al. 2003

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Streptozocin (STZ)-induced diabetic rats show hyperalgesia that is partially attributed to altered protein kinase C (PKC) activity. Both attenuated neuronal nitric oxide synthase (nNOS)-cGMP system and tetrodotoxin-resistant (TTX-R) Na channels in dorsal root ganglion neurons may be involved in diabetic hyperalgesia. We examined whether PKC␤ inhibition ameliorates diabetic hyperalgesia and, if so, whether the effect is obtained through action on neurons by testing nociceptive threshold in normal and STZ-induced diabetic rats treated with or without PKC␤-selective inhibitor LY333531 (LY) and by assessing the implication of LY in either nNOS-cGMP system or TTX-R Na channels of isolated dorsal root ganglion neurons. The decreased nociceptive threshold in diabetic rats was improved either after 4 weeks of LY treatment or with a single intradermal injection into the footpads. The treatment of LY for 6 weeks significantly decreased p-PKC␤ and ameliorated a decrease in cGMP content in dorsal root ganglia of diabetic rats. The latter effect was confirmed in ex vivo condition. The treatment with NO donor for 4 weeks also normalized both diabetic hyperalgesia and decreased cGMP content in dorsal root ganglions. The expressions of nNOS and TTX-R Na channels were not changed with LY treatment. These results suggest that LY is effective for treating diabetic hyperalgesia through ameliorating the decrease in the nNOS-cGMP system.

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“…In diabetic BB/W rats, a model for autoimmune-mediated type I diabetes, up-regulation of HVA Ca 2+ current amplitude by about twofold occurred in small nociceptive DRG cells, consequently decreasing opioid-induced inhibition of HVA currents (Hall et al, 1996;. BB/W rats, after 8 months in a diabetic state, similarly up-regulated T-channels in small DRG cells (Hall et al, 1995).…”

Section: Diabetic Neuropathymentioning

confidence: 97%

T‐type voltage‐gated calcium channels as targets for the development of novel pain therapies

Todorović

Jevtović-Todorović

2011

British J Pharmacology

153

135

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It is well recognized that voltage‐gated calcium (Ca2+) channels modulate the function of peripheral and central pain pathways by influencing fast synaptic transmission and neuronal excitability. In the past, attention focused on the modulation of different subtypes of high‐voltage‐activated‐type Ca2+ channels; more recently, the function of low‐voltage‐activated or transient (T)‐type Ca2+ channels (T‐channels) in nociception has been well documented. Currently, available pain therapies remain insufficient for certain forms of pain associated with chronic disorders (e.g. neuropathic pain) and often have serious side effects. Hence, the identification of selective and potent inhibitors and modulators of neuronal T‐channels may help greatly in the development of safer, more effective pain therapies. Here, we summarize the available information implicating peripheral and central T‐channels in nociception. We also discuss possible future developments aimed at selective modulation of function of these channels, which are highly expressed in nociceptors.

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Opiate-mediated inhibition of calcium signaling is decreased in dorsal root ganglion neurons from the diabetic BB/W rat.

Abstract: The effect of diabetes mellitus on opiate-mediated inhibition of calcium current density (I DCa [

Cited by 41 publications

References 45 publications

CaV1.2 and CaV1.3 channel hyperactivation in mouse islet β cells exposed to type 1 diabetic serum

CaV1.2 and CaV1.3 channel hyperactivation in mouse islet β cells exposed to type 1 diabetic serum

Protein Kinase Cβ Selective Inhibitor LY333531 Attenuates Diabetic Hyperalgesia Through Ameliorating cGMP Level of Dorsal Root Ganglion Neurons

T‐type voltage‐gated calcium channels as targets for the development of novel pain therapies

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