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n-Alcohols Control Neuronal Excitability through Differential Modulation of Nav and Kv7 Channels
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| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | 서병창 | - |
| dc.contributor.author | Da-Jeong Jeong | - |
| dc.date.accessioned | 2026-09-01T19:29:19Z | - |
| dc.date.available | 2026-09-01T19:29:19Z | - |
| dc.date.issued | 2026 | - |
| dc.identifier.uri | https://scholar.dgist.ac.kr/handle/20.500.11750/60716 | - |
| dc.identifier.uri | http://dgist.dcollection.net/common/orgView/200001012568 | - |
| dc.description | Kv7 channel, n-alcohols, PI(4,5)P₂, SCG neuron, Nav channel | - |
| dc.description.tableofcontents | I. INTRODUCTION 1 II. MATERIALS AND METHODS 17 2.1. Cell culture and transfection 17 2.2. SCG neuronal preparations 17 2.3. Animals 18 2.4. Electrophysiological recording 18 2.5. Non-stationary noise analysis 19 2.6. Solution and materials 20 2.7. Molecular cloning 21 2.8. Reverse Transcription-PCR 21 2.9. Single-cell RNA sequencing data analysis 22 2.10. Data analysis and statistical analysis 22 III. RESULTS 24 3.1. Dual regulation of Kv7.2/7.3 channels by long-chain n-alcohols 24 3.1.1. Short-chain n-alcohols inhibit while long chain n-alcohols activate Kv7 currents in cultured SCG neurons 24 3.1.2. n-Alcohols differentially modulate heterologous Kv7.2/7.3 channels expressed in tsA-201 cells 27 3.1.3. Long-chain n-alcohols shift the voltage dependence of Kv7.2/7.3 channels, similar to retigabine 30 3.1.4. Hexanol differentially regulates current amplitude and voltage dependence of Kv7 channel subtypes 33 3.1.5. HeOH increases the maximal open probability of Kv7.2/7.3 channels without changing single-channel conductance and channel number 38 3.1.6. HeOH accelerates activation and slow deactivation of Kv7 channels in a subtype- specific manner 40 3.1.7. Generation and validation of the W236L mutant on Kv7.2 channel 42 3.1.8. The stimulatory action of HeOH depends on the conserved W236 residue 44 3.1.9. The inhibitory action of EtOH is independent of the W236 residue 51 3.1.10. Kv7.1 channels lacking the conserved S5 tryptophan are inhibited by both short- and long-chain n-alcohols 53 3.1.11. n-Alcohols regulate Kv7 channels through two functionally separable regulatory sites 56 3.1.12. The hydroxyl group with negative electrostatic potential is essential for n-alcohol action on Kv7 channels 61 3.1.13. Recording stability and PI(4,5)P2-dependent gating axis of hexanol action on Kv7.2/7.3 channels 66 3.2. Kv7 channels as an important contributor to alcohol-induced modulation of neuronal excitability in neonatal rat superior cervical ganglion 69 3.2.1. n-Alcohols differentially regulate AP firing and resting membrane potential in SCG neurons in a chain length-dependent manner 69 3.2.2. Both EtOH and HeOH suppress voltage-gated sodium currents in SCG neurons 74 3.2.3. Kv7 currents in SCG neurons are oppositely regulated by EtOH and HeOH 77 3.2.4. Selective Kv7 inhibition, but not selective NaV inhibition, reproduces the AP firing increase induced by EtOH 79 3.2.5. Selective Kv7 activation, but not selective NaV inhibition, reproduces the AP firing suppression induced by HeOH 84 3.2.6. Combined NaV and Kv7 modulation reproduces the broader AP phenotypes induced by EtOH and HeOH 87 3.2.7. NaV1.7 is the predominant sodium channel subtype in SCG neurons 90 3.2.8. Selective NaV1.7 inhibition does not alter AP firing despite substantial sodium current reduction 93 3.2.9. Moderate sodium current inhibition by TTX is insufficient to alter AP firing 98 3.2.10. Summary model, Kv7 channel modulation determines the direction of alcohol- induced firing changes 102 IV. DISCUSSION 105 V. REFERENCES 115 VI. 국문요약 124 |
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| dc.format.extent | 127 | - |
| dc.language | eng | - |
| dc.publisher | DGIST | - |
| dc.title | n-Alcohols Control Neuronal Excitability through Differential Modulation of Nav and Kv7 Channels | - |
| dc.title.alternative | Nav 및 Kv7 채널의 차등적 조절을 통한 n-알코올의 신경흥분성 조절 | - |
| dc.type | Thesis | - |
| dc.identifier.doi | 10.22677/THESIS.200001012568 | - |
| dc.description.degree | Doctor | - |
| dc.contributor.department | Department of Brain Sciences | - |
| dc.contributor.coadvisor | Hyun-Ho Lim | - |
| dc.date.awarded | 2026-08-01 | - |
| dc.publisher.location | Daegu | - |
| dc.description.database | dCollection | - |
| dc.citation | XT.BD 정22 202608 | - |
| dc.date.accepted | 2026-07-21 | - |
| dc.contributor.alternativeDepartment | 뇌과학과 | - |
| dc.subject.keyword | Kv7 channel, n-alcohols, PI(4,5)P₂, SCG neuron, Nav channel | - |
| dc.contributor.affiliatedAuthor | Da-Jeong Jeong | - |
| dc.contributor.affiliatedAuthor | Byung-Chang Suh | - |
| dc.contributor.affiliatedAuthor | Hyun-Ho Lim | - |
| dc.contributor.alternativeName | 정다정 | - |
| dc.contributor.alternativeName | Byung-Chang Suh | - |
| dc.contributor.alternativeName | 임현호 | - |
| dc.rights.embargoReleaseDate | 2027-02-28 | - |
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