Ethanol Effect on BK Channels is Modulated by Magnesium.
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 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. 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.
Institute of Neurobiology UPR-MSC, San Juan, Puerto Rico.
Héctor G
HG
Marrero
Institute of Neurobiology UPR-MSC, San Juan, Puerto Rico.
Steven N
SN
Treistman
Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts.
José R
JR
Lemos
D000818:Animals; D002478:Cells, Cultured; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism*; D051381:Rats
D051036:Large-Conductance Calcium-Activated Potassium Channels; D000431:Ethanol; D008274:Magnesium
BK Channel; Ethanol; Magnesium