CREB regulation of BK channel gene expression underlies rapid drug tolerance

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CREB regulation of BK channel gene expression underlies rapid drug tolerance.

Pharmacodynamic tolerance is believed to involve homeostatic mechanisms initiated to restore normal neural function. Drosophila exposed to a sedating dose of an organic solvent, such as benzyl alcohol or ethanol, acquire tolerance to subsequent sedation by that solvent. The slo gene encodes BK-type Ca(2+)-activated K(+) channels and has been linked to alcohol- and organic solvent-induced behavi...

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slo K(+) channel gene regulation mediates rapid drug tolerance.

Changes in neural activity caused by exposure to drugs may trigger homeostatic mechanisms that attempt to restore normal neural excitability. In Drosophila, a single sedation with the anesthetic benzyl alcohol changes the expression of the slo K(+) channel gene and induces rapid drug tolerance. We demonstrate linkage between these two phenomena by using a mutation and a transgene. A mutation th...

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Posttranscriptional Regulation of BK Channel Splice Variant Stability by miR-9 Underlies Neuroadaptation to Alcohol

Tolerance represents a critical component of addiction. The large-conductance calcium- and voltage-activated potassium channel (BK) is a well-established alcohol target, and an important element in behavioral and molecular alcohol tolerance. We tested whether microRNA, a newly discovered class of gene expression regulators, plays a role in the development of tolerance. We show that in adult mam...

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Lipid regulation of BK channel function

This mini-review focuses on lipid modulation of BK (MaxiK, BKCa) current by a direct interaction between lipid and the BK subunits and/or their immediate lipid environment. Direct lipid-BK protein interactions have been proposed for fatty and epoxyeicosatrienoic acids, phosphoinositides and cholesterol, evidence for such action being less clear for other lipids. BK α (slo1) subunits are suffici...

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Large conductance voltage- and Ca(2+)-activated potassium channels (BK channels) are important feedback regulators in excitable cells and are potently regulated by protein kinases. The present study reveals a dual role of protein kinase C (PKC) on BK channel regulation. Phosphorylation of S(695) by PKC, located between the two regulators of K(+) conductance (RCK1/2) domains, inhibits BK channel...

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ژورنال

عنوان ژورنال: Genes, Brain and Behavior

سال: 2009

ISSN: 1601-1848,1601-183X

DOI: 10.1111/j.1601-183x.2009.00479.x