Statins and fibrate target ClC-1 - from side effects to CLC pharmacology.
Lipid-lowering drugs have been associated with severe adverse effects on skeletal muscle, including rhabdomyolysis. More common symptoms include cramps and myalgia. In this issue of the BJP, Pierno et al. find that two statins and fenofibrate, often used in combination, decrease function of the chloride channel member 1 of the mammalian CLC protein family of chloride channels and transporters in skeletal muscle by three distinct mechanisms. Other compounds have recently been shown to potently modulate the pharmacologically less well-explored CLC protein family, which comprises chloride channels and chloride/proton antiporters. These findings may well lead to a new era of CLC protein pharmacology.
Zdebik
Anselm A
AA
London Epithelial Group, Royal Free Campus, University College London, Department of Neuroscience, Physiology and Pharmacology, London, UK. a.zdebik@ucl.ac.uk
D000200:Action Potentials; D000818:Animals; D000069059:Atorvastatin; D002118:Calcium / Q000378:metabolism; D018118:Chloride Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D015536:Down-Regulation; D004789:Enzyme Activation; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology* / Q000633:toxicity; D011345:Fenofibrate / Q000494:pharmacology* / Q000633:toxicity; D000077340:Fluvastatin; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000633:toxicity; D007211:Indoles / Q000494:pharmacology* / Q000633:toxicity; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology* / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism
C086321:CLC-1 channel; D018118:Chloride Channels; D002712:Chlorides; D005229:Fatty Acids, Monounsaturated; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D007211:Indoles; D011758:Pyrroles; D012333:RNA, Messenger; D000077340:Fluvastatin; D000069059:Atorvastatin; D011493:Protein Kinase C; D002118:Calcium; D011345:Fenofibrate