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• W1946398012 abstract "Background The large conductance Ca 2+ ‐ and voltage‐activated K + channel ( BK ) is an important player in molecular and behavioral alcohol tolerance. Trafficking and surface expression of ion channels contribute to the development of addictive behaviors. We have previously reported that internalization of the BK channel is a component of molecular tolerance to ethanol (EtOH). Methods Using primary cultures of hippocampal neurons, we combine total internal reflection fluorescence microscopy, electrophysiology, and biochemical techniques to explore how exposure to Et OH affects the expression and subcellular localization of endogenous BK channels over time. Results Exposure to Et OH changed the expression of endogenous BK channels in a time‐dependent manner at the perimembrane area (plasma membrane and/or the area adjacent to it), while total protein levels of BK remain unchanged. These results suggest a redistribution of the channel within the neurons rather than changes in synthesis or degradation rates. Our results showed a temporally nonlinear effect of Et OH on perimembrane expression of BK . First, there was an increase in BK perimembrane expression after 10 minutes of Et OH exposure that remained evident after 3 hours, although not correlated to increases in functional channel expression. In contrast, after 6 hours of Et OH exposure, we observed a significant decrease in both BK perimembrane expression and functional channel expression. Furthermore, after 24 hours of Et OH exposure, perimembrane levels of BK had returned to baseline. Conclusions We report a complex time‐dependent pattern in the effect of Et OH on BK channel trafficking, including successive increases and decreases in perimembrane expression and a reduction in active BK channels after 3 and 6 hours of Et OH exposure. Possible mechanisms underlying this multiphasic trafficking are discussed. As molecular tolerance necessarily underlies behavioral tolerance, the time‐dependent alterations we see at the level of the channel may be relevant to the influence of drinking patterns on the development of behavioral tolerance." @default.
• W1946398012 created "2016-06-24" @default.
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• W1946398012 date "2015-08-06" @default.
• W1946398012 modified "2023-10-16" @default.
• W1946398012 title "Time-Dependent Effects of Ethanol on BK Channel Expression and Trafficking in Hippocampal Neurons" @default.
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• W1946398012 doi "https://doi.org/10.1111/acer.12808" @default.
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