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Ethanol Effect on BK Channels is Modulated by Magnesium
Author(s) -
Marrero Héctor G.,
Treistman Steven N.,
Lemos José R.
Publication year - 2015
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12821
Subject(s) - magnesium , bk channel , ethanol , chemistry , biophysics , calcium , biochemistry , biology , organic chemistry
Background 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. Methods Using outside‐out patches from hippocampal neuronal cultures, we examined the consequences of altered intracellular Mg 2+ on the effects that EtOH has on BK channels. Results We find that the effect of EtOH is bimodally influenced by the Mg 2+ concentration on the cytoplasmic side. More specifically, when internal Mg 2+ concentrations are ≤200 μ M, 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. When patches are made with the actin destabilizer cytochalasin D present on the cytoplasmic side, the potentiation caused by EtOH becomes independent of the Mg 2+ concentration. Furthermore, in the presence of the actin stabilizer phalloidin, EtOH causes inhibition even at Mg 2+ concentrations of 1 mM. Conclusions Internal Mg 2+ 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 Mg 2+ observed in frequent/chronic drinkers would decrease EtOH's actions on synaptic (e.g., actin‐bound) BK channels, producing a form of molecular tolerance.