Inhibition of high-conductance, calcium-activated potassium channels of rabbit colon epithelium by magnesium.
High-conductance, Ca(2+)-activated K+ channels from the basolateral membrane of rabbit distal colon epithelial cells were reconstituted into planar phospholipid bilayers to examine the effect of Mg2+ on the single-channel properties. Mg2+ decreases channel current and conductance in a concentration-dependent manner from both the cytoplasmic and the extracellular side of the channel. In contrast to other K+ channels, Mg2+ does not cause rectification of current through colonic Ca(2+)-activated K+ channels. In addition, cytoplasmic Mg2+ decreases the reversal potential of the channel. The Mg(2+)-induced decrease in channel conductance is relieved by high K+ concentrations, indicating competitive interaction between K+ and Mg2+. The monovalent organic cation choline also decreases channel conductance and reversal potential, suggesting that the effect is unspecific. The inhibition of channel current by Mg2+ and choline most likely is a result of electrostatic screening of negative charges located superficially in the channel entrance. But in addition to charge, other properties appear to be necessary for channel inhibition, as Na+ and Ba2+ are no (or only weak) inhibitors. Mg2+ and possibly other cations may play a role in the regulation of current through these channels.
Wachter
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Pharmakologisches Institut, Universität Wien, Vienna, Austria.
Turnheim
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K
D000818:Animals; D003106:Colon / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008051:Lipid Bilayers; D008274:Magnesium / Q000494:pharmacology*; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects; D024681:Potassium Channels, Calcium-Activated; D011817:Rabbits
D007473:Ion Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008051:Lipid Bilayers; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D008274:Magnesium