Dysfunction of Small-Conductance Ca2+-Activated Potassium (SK) Channels Drives Amygdala Hyperexcitability and Neuropathic Pain Behaviors: Involvement of Epigenetic Mechanisms
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Neuropathic Pain Model
2.3. Behavior
2.3.1. Mechanosensitivity
2.3.2. Vocalizations
2.4. Electrophysiology
2.4.1. Brain Slice Preparation
2.4.2. Patch-Clamp Recording of CeA Neurons in the Right Amygdala
2.5. Drugs and Drug Application
2.5.1. Behavioral Experiments
2.5.2. Brain Slice Experiments
2.6. Histology
2.6.1. Verification of Microdialysis Probe Locations
2.6.2. Immunohistochemistry for SK2 Protein Detection in the Right CeLC
2.7. Molecular Biology Experiments
2.7.1. Tissue Preparation
2.7.2. Western Blotting
2.7.3. Reverse Transcription Polymerase Chain Reaction (RT-PCR)
2.7.4. Bisulfite Conversion of DNA and Methylation-Specific PCR
2.7.5. Bisulfite Sequencing Specific PCR and Cloning
2.7.6. Bisulfite DNA Sequencing and Analysis
2.8. Statistical Analysis and Scientific Rigor
3. Results
3.1. Loss of SK Channel-Mediated Control of Pain Behaviors and Neuronal Excitability in Neuropathic Pain
3.2. Loss of SK Channel Function (mAHP) in Regular-Firing Amygdala Neurons in Neuropathic Pain
3.3. Selective SK Channel Activation Inhibits Neuropathic Pain Behaviors Due to Partial Rescue of mAHP
3.4. Decreased SK2 Subunit Expression in Neuropathic Pain State Is Localized to CeA
3.5. DNA Methylation Profile of CpG Island in the SK2 Gene Promoter Region in CeA
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Methylation-Specific Primers | Sequence | Amplicon Size |
M1-left | GGGTAGTTAGTTTAATGTGAGCGA | 102 bp |
M1-right | TAATAATACAAAAAAACGAACGCG | |
U1-left | GGGGTAGTTAGTTTAATGTGAGTGA | 102 bp |
U1-right | AATAATACAAAAAAACAAACACAAA | |
M2-left | GTGCGTTTAATTAATCGGATTC | 120 bp |
M2-right | GATAATACACCCTACGCAATACGTT | |
U2-left | TTGGTGTGTTTAATTAATTGGATTT | 124 bp |
U2-right | CAATAATACACCCTACACAATACATT | |
Bisulfite-Specific Primers | ||
BSP-F1 | AGGGGTTTTTATTTTGTAGG | 285 bp |
BSP-R1 | ACAATAAAATTTCCATATCAAACCTAT | |
BSP-F2 | AATAGGTTTGATATGGAAATTTTA | 287 bp |
BSP-R2 | AACAACAAAAACAAATTATCCCC |
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Yakhnitsa, V.; Thompson, J.; Ponomareva, O.; Ji, G.; Kiritoshi, T.; Mahimainathan, L.; Molehin, D.; Pruitt, K.; Neugebauer, V. Dysfunction of Small-Conductance Ca2+-Activated Potassium (SK) Channels Drives Amygdala Hyperexcitability and Neuropathic Pain Behaviors: Involvement of Epigenetic Mechanisms. Cells 2024, 13, 1055. https://doi.org/10.3390/cells13121055
Yakhnitsa V, Thompson J, Ponomareva O, Ji G, Kiritoshi T, Mahimainathan L, Molehin D, Pruitt K, Neugebauer V. Dysfunction of Small-Conductance Ca2+-Activated Potassium (SK) Channels Drives Amygdala Hyperexcitability and Neuropathic Pain Behaviors: Involvement of Epigenetic Mechanisms. Cells. 2024; 13(12):1055. https://doi.org/10.3390/cells13121055
Chicago/Turabian StyleYakhnitsa, Vadim, Jeremy Thompson, Olga Ponomareva, Guangchen Ji, Takaki Kiritoshi, Lenin Mahimainathan, Deborah Molehin, Kevin Pruitt, and Volker Neugebauer. 2024. "Dysfunction of Small-Conductance Ca2+-Activated Potassium (SK) Channels Drives Amygdala Hyperexcitability and Neuropathic Pain Behaviors: Involvement of Epigenetic Mechanisms" Cells 13, no. 12: 1055. https://doi.org/10.3390/cells13121055
APA StyleYakhnitsa, V., Thompson, J., Ponomareva, O., Ji, G., Kiritoshi, T., Mahimainathan, L., Molehin, D., Pruitt, K., & Neugebauer, V. (2024). Dysfunction of Small-Conductance Ca2+-Activated Potassium (SK) Channels Drives Amygdala Hyperexcitability and Neuropathic Pain Behaviors: Involvement of Epigenetic Mechanisms. Cells, 13(12), 1055. https://doi.org/10.3390/cells13121055