1. Ethanol Effect on BK Channels is Modulated by Magnesium
- Author
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Marrero, Héctor G., Treistman, Steven N., and Lemos, José R.
- Abstract
Alcoholics have been reported to have reduced levels of magnesium in both their extracellular and intracellular compartments. Calcium‐dependent potassium channels (BK) are known to be one of ethanol (EtOH)’s better known molecular targets. Using outside‐out patches from hippocampal neuronal cultures, we examined the consequences of altered intracellular Mg2+on the effects that EtOH has on BK channels. We find that the effect of EtOH is bimodally influenced by the Mg2+concentration on the cytoplasmic side. More specifically, when internal Mg2+concentrations are ≤200 μM, EtOH decreases BK activity, whereas it increases activity when Mg2+is at 1 mM. Similar results are obtained when using patches from HEK cells expressing only the α‐subunit of BK. When patches are made with the actin destabilizer cytochalasin D present on the cytoplasmic side, the potentiation caused by EtOH becomes independent of the Mg2+concentration. Furthermore, in the presence of the actin stabilizer phalloidin, EtOH causes inhibition even at Mg2+concentrations of 1 mM. Internal Mg2+can modulate the EtOH effects on BK channels only when there is an intact, internal actin interaction with the channel, as is found at synapses. We propose that the EtOH‐induced decrease in cytoplasmic Mg2+observed in frequent/chronic drinkers would decrease EtOH's actions on synaptic (e.g., actin‐bound) BK channels, producing a form of molecular tolerance.
- Published
- 2015
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