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- W2078484265 abstract "Ethanol levels reached in circulation during moderate-heavy alcohol intoxication (50 mM) modify BK channel steady-state activity (NPo) eventually altering physiology and behavior. In general, ethanol decreases NPo of vascular smooth muscle BK channels while increasing NPo of neuronal BK channels. Channel subunit composition, posttranslational modification and channel lipid microenvironment all play a role in alcohol final effect (Brodie et al., 2007). However, ethanol action on BK NPo solely requires the channel-forming subunit (slo1) and is function of activating ion (i.e., Ca2+i) (Liu et al., 2008; Bukiya et al., 2009). Whether activating ion-dependence of alcohol action is unique to slo1 or, rather, extends to the other members of the slo family remains unknown. Slo2.1 (Slick), Slo2.2 (Slack), and Slo3 gene products render ion channel proteins that display a phenotype common to slo1: high conductance for K+ and dual regulation of gating by transmembrane voltage and intracellular ion-recognition, with slo2 and slo3 being activated by Na+i and OH−i, respectively (Salkoff et al., 2006). Here, after expression in Xenopus oocytes, we probed cbv1, slick/slack and slo3 channels with 50 mM ethanol over a wide range of activating ion concentration in inside-out patches. Thus, we constructed conductance-voltage plots from macroscopic current or measured NPo from single channel recordings. Ethanol-induced potentiation of cbv1 currents turned into inhibition as Ca2+i increased, with a crossover at ∼20 μM Ca2+i. In contrast, slo2 and slo3 channels remained resistant to 50 mM ethanol even when probed at a wide concentration range of activating ion: 10-140 mM Na+i (slo2) and 0.01-10 μM OH−i (slo3). Data underscore that the ethanol-sensitivity and its ligand-dependence found in slo1 channels are not extensive to other members of the slo channel family, suggesting selective interaction(s) between Ca2+-sensing and ethanol-sensing mechanisms. Support: R37AA011560 (AMD)" @default.
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- W2078484265 date "2013-01-01" @default.
- W2078484265 modified "2023-09-30" @default.
- W2078484265 title "Activating Ion Determines Differential Ethanol-Sensitivity of Slo Family Channels" @default.
- W2078484265 doi "https://doi.org/10.1016/j.bpj.2012.11.2610" @default.
- W2078484265 hasPublicationYear "2013" @default.
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