Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Zoga, V; Kawano, T; Liang, MY; Bienegraeber, M; Weihrauch, D; McCallum, B; Gemes, G; Hogan, Q; Sarantopoulos, C.
K-ATP channel subunits in rat dorsal root ganglia: alterations by painful axotomy.
Mol Pain. 2010; 6:6-6
Doi: 10.1186/1744-8069-6-6
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- Gemes Geza
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- Abstract:
- Background: ATP-sensitive potassium (K-ATP) channels in neurons mediate neuroprotection, they regulate membrane excitability, and they control neurotransmitter release. Because loss of DRG neuronal K-ATP currents is involved in the pathophysiology of pain after peripheral nerve injury, we characterized the distribution of the K-ATP channel subunits in rat DRG, and determined their alterations by painful axotomy using RT-PCR, immunohistochemistry and electron microscopy. Results: PCR demonstrated Kir6.1, Kir6.2, SUR1 and SUR2 transcripts in control DRG neurons. Protein expression for all but Kir6.1 was confirmed by Western blots and immunohistochemistry. Immunostaining of these subunits was identified by fluorescent and confocal microscopy in plasmalemmal and nuclear membranes, in the cytosol, along the peripheral fibers, and in satellite glial cells. Kir6.2 co-localized with SUR1 subunits. Kir6.2, SUR1, and SUR2 subunits were identified in neuronal subpopulations, categorized by positive or negative NF200 or CGRP staining. K-ATP current recorded in excised patches was blocked by glybenclamide, but preincubation with antibody against SUR1 abolished this blocking effect of glybenclamide, confirming that the antibody targets the SUR1 protein in the neuronal plasmalemmal membrane. In the myelinated nerve fibers we observed anti-SUR1 immunostaining in regularly spaced funneled-shaped structures. These structures were identified by electron microscopy as Schmidt-Lanterman incisures (SLI) formed by the Schwann cells. Immunostaining against SUR1 and Kir6.2 colocalized with anti-Caspr at paranodal sites. DRG excised from rats made hyperalgesic by spinal nerve ligation exhibited similar staining against Kir6.2, SUR1 or SUR2 as DRG from controls, but showed decreased prevalence of SUR1 immunofluorescent NF200 positive neurons. In DRG and dorsal roots proximal to axotomy SLI were smaller and showed decreased SUR1 immunofluorescence. Conclusions: We identified Kir6.2/SUR1 and Kir6.2/SUR2 K-ATP channels in rat DRG neuronal somata, peripheral nerve fibers, and glial satellite and Schwann cells, in both normal state and after painful nerve injury. This is the first report of K-ATP channels in paranodal sites adjacent to nodes of Ranvier and in the SLI of the Schwann cells. After painful axotomy K-ATP channels are downregulated in large, myelinated somata and also in SLI, which are also of smaller size compared to controls. Because K-ATP channels may have diverse functional roles in neurons and glia, further studies are needed to explore the potential of K-ATP channels as targets of therapies against neuropathic pain and neurodegeneration.
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- ATP-Binding Cassette Transporters - genetics
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