Title

n-Alcohols Control Neuronal Excitability through Differential Modulation of Nav and Kv7 Channels

Alternative Title

Nav 및 Kv7 채널의 차등적 조절을 통한 n-알코올의 신경흥분성 조절

DGIST Authors

Da-Jeong Jeong ; Byung-Chang Suh ; Hyun-Ho Lim

Advisor

서병창

Co-Advisor(s)

Hyun-Ho Lim

Issued Date

2026

Awarded Date

2026-08-01

Type

Thesis

Description

Kv7 channel, n-alcohols, PI（4,5）P₂, SCG neuron, Nav channel

Table Of Contents

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

URI

https://scholar.dgist.ac.kr/handle/20.500.11750/60716
http://dgist.dcollection.net/common/orgView/200001012568

DOI

10.22677/THESIS.200001012568

Degree

Doctor

Department

Department of Brain Sciences

Publisher

DGIST

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