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Ethanol inhibits Kv7.2/7.3 channel open probability by reducing the PI(4,5)P-2 sensitivity of Kv7.2 subunit

Title
Ethanol inhibits Kv7.2/7.3 channel open probability by reducing the PI(4,5)P-2 sensitivity of Kv7.2 subunit
Authors
Kim, Kwon WooSuh, Byung-Chang
DGIST Authors
Kim, Kwon Woo; Suh, Byung-Chang
Issue Date
2021-06
Citation
BMB Reports, 54(6), 311-316
Type
Article
Author Keywords
EthanolKv7.2/7.3 channelOpen probabilityPI(4,5)P-2Tetraethylammonium
Keywords
NONSTATIONARY NOISE-ANALYSISACTIVATES KCNQ CHANNELSPOTASSIUM CHANNELK+ CHANNELSPIP2MODULATIONRECEPTORALCOHOLEXCITABILITYKCNQ2/KCNQ3
ISSN
1976-6696
Abstract
Ethanol often causes critical health problems by altering the neuronal activities of the central and peripheral nerve systems. One of the cellular targets of ethanol is the plasma membrane proteins including ion channels and receptors. Recently, we reported that ethanol elevates membrane excitability in sympathetic neurons by inhibiting Kv7.2/7.3 channels in a cell type-specific manner. Even though our studies revealed that the inhibitory effects of ethanol on the Kv7.2/7.3 channel was diminished by the increase of plasma membrane phosphatidylinositol 4,5-bisphosphate (PI (4,5)P-2), the molecular mechanism of ethanol on Kv7.2/7.3 channel inhibition remains unclear. By investigating the kinetics of Kv7.2/7.3 current in high K+ solution, we found that ethanol inhibited Kv7.2/7.3 channels through a mechanism distinct from that of tetraethylammonium (TEA) which enters into the pore and blocks the gate of the channels. Using a non-stationary noise analysis (NSNA), we demonstrated that the inhibitory effect of ethanol is the result of reduction of open probability (P-O) of the Kv7.2/7.3 channel, but not of a single channel current (i) or channel number (N). Finally, ethanol selectively facilitated the kinetics of Kv7.2 current suppression by voltage-sensing phosphatase (VSP)-induced PI(4,5)P-2 depletion, while it slowed down Kv7.2 current recovery from the VSP-induced inhibition. Together our results suggest that ethanol regulates neuronal activity through the reduction of open probability and PI(4,5)P-2 sensitivity of Kv7.2/7.3 channels.
URI
http://hdl.handle.net/20.500.11750/13996
DOI
10.5483/BMBRep.2021.54.6.231
Publisher
The Biochemical Society of the Republic of Korea
Related Researcher
  • Author Suh, Byung-Chang Laboratory of Brain Signal and Synapse Research
  • Research Interests Molecular mechanisms of epilepsy and sensory pain transmission; Signaling mechanism of ion channel regulation and membrane excitability; 분자전기생리; 간질 및 통증의 분자적 기전 연구
Files:
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Collection:
Department of Brain SciencesLaboratory of Brain Signal and Synapse Research1. Journal Articles


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