Possible Interaction: Ethanol and Berkelium

“Brief (several minutes) ethanol exposure usually leads to increased BK current, which results from ethanol interaction with a pocket mapped to the BK channel-forming slo1 protein cytosolic tail domain.”

“EtOH activates BK when magnesium levels are nearer to normal (1 mM), while EtOH actually inhibits BK when magnesium levels are reduced (200 lM).”

“In contrast, we note that other groups have found divergent results, for example, where EtOH actually inhibits BK function in central amygdala neurons (Li et al., 2014).”

“Marrero and colleagues (2015) have added to our understanding of the regulation of BK by EtOH , and provided novel evidence that the ability of EtOH to excite BK is strongly regulated by magnesium levels and the actin cytoskeleton.”

“Thus, the activation of BK by EtOH could reduce excitability and, in this way, may contribute to the intoxicating, sedating, or other acute effects of EtOH exposure.”

“Using this method, Marrero and colleagues (2015) found that the ability of EtOH to activate BK is strongly regulated by magnesium levels.”

“Moreover, in vitro studies document that BK activity is modified by ethanol with an EC50~23 mM, which is near blood alcohol levels considered legal intoxication in most states of the USA (0.08 g/dL = 17.4 mM).”

“Twenty-four hour exposure to 25 mM ethanol resulted in a down-regulation of BK current in hSlo and hSlo + beta(4) channels, but not in hSlo + beta(1) channels.”

“More specifically, when internal Mg(2+) concentrations are ≤200 μM, EtOH decreases BK activity, whereas it increases activity when Mg(2+) is at 1 mM. Similar results are obtained when using patches from HEK cells expressing only the α-subunit of BK.”

“In contrast, after 6 hours of EtOH exposure, we observed a significant decrease in both BK perimembrane expression and functional channel expression.”

“Our results showed a temporally nonlinear effect of EtOH on perimembrane expression of BK.”

“ Ethanol alters BK (slo1) channel function leading to perturbation of physiology and behavior.”

“ EtOH at 0.3% vol/vol (~50 mM) enhanced whole cell BK currents at +30 mV and above, determined by the selective BK channel blocker paxilline.”

“Remarkably, ethanol inhibition of cbv1+&bgr;1 in bilayers and wt mouse VSMC BK were drastically blunted by cholesterol depletion.”

“Using BK channel‐forming (cbv1) subunits from cerebral artery myocytes, we demonstrate that EtOH potentiates and inhibits current at Ca i 2 + lower and higher than ∼15 μM, respectively.”