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BK Ca Channel Inhibition by Peripheral Nerve Injury Is Restored by the Xanthine Derivative KMUP-1 in Dorsal Root Ganglia.
- Source :
-
Cells [Cells] 2021 Apr 20; Vol. 10 (4). Date of Electronic Publication: 2021 Apr 20. - Publication Year :
- 2021
-
Abstract
- This study explored whether KMUP-1 improved chronic constriction injury (CCI)-induced BK <subscript>Ca</subscript> current inhibition in dorsal root ganglion (DRG) neurons. Rats were randomly assigned to four groups: sham, sham + KMUP-1, CCI, and CCI + KMUP-1 (5 mg/kg/day, i.p.). DRG neuronal cells (L4-L6) were isolated on day 7 after CCI surgery. Perforated patch-clamp and inside-out recordings were used to monitor BK <subscript>Ca</subscript> currents and channel activities, respectively, in the DRG neurons. Additionally, DRG neurons were immunostained with anti-NeuN, anti-NF200 and anti-BK <subscript>Ca</subscript> . Real-time PCR was used to measure BK <subscript>Ca</subscript> mRNA levels. In perforated patch-clamp recordings, CCI-mediated nerve injury inhibited BK <subscript>Ca</subscript> currents in DRG neurons compared with the sham group, whereas KMUP-1 prevented this effect. CCI also decreased BK <subscript>Ca</subscript> channel activity, which was recovered by KMUP-1 administration. Immunofluorescent staining further demonstrated that CCI reduced BK <subscript>Ca</subscript> -channel proteins, and KMUP-1 reversed this. KMUP-1 also changed CCI-reduced BK <subscript>Ca</subscript> mRNA levels. KMUP-1 prevented CCI-induced neuropathic pain and BK <subscript>Ca</subscript> current inhibition in a peripheral nerve injury model, suggesting that KMUP-1 could be a potential agent for controlling neuropathic pain.
- Subjects :
- Animals
Chronic Disease
Constriction, Pathologic
Ganglia, Spinal drug effects
Gene Expression Regulation drug effects
Ion Channel Gating drug effects
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits genetics
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits metabolism
Male
Neurons drug effects
Neurons metabolism
Peripheral Nerve Injuries pathology
RNA, Messenger genetics
RNA, Messenger metabolism
Rats, Sprague-Dawley
Rats
Ganglia, Spinal metabolism
Large-Conductance Calcium-Activated Potassium Channel alpha Subunits antagonists & inhibitors
Peripheral Nerve Injuries metabolism
Piperidines pharmacology
Xanthines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2073-4409
- Volume :
- 10
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cells
- Publication Type :
- Academic Journal
- Accession number :
- 33923953
- Full Text :
- https://doi.org/10.3390/cells10040949