Ion channel formation by duramycin.
The formation of ion channels by the nonadecapeptide antibiotic duramycin was examined using black lipid membranes and using the patch-clamp technique. In black lipid membranes made from glyceryl monooleate or a phosphatidylcholine/phosphatidylethanolamine mixture, duramycin induced complex fluctuations in membrane conductance, some step-like and some which were incapable of being resolved into discrete conductance states. Both conductance and largest step size increased with time. A similar time-dependent increase in conductance was seen in patch-clamp experiments with HCA-7 Colony 29 human colonic epithelial cell. The channels displayed weak anion selectivity and the smaller channels formed in patches from epithelial cells showed weak inward-rectification. Channel formation by duramycin was achieved at lower concentrations when the black lipid membrane was made with phospholipid rather than with glyceryl monooleate. Lower concentrations were effective in generating conductances in epithelial cells than in bilayers. It is concluded that duramycin forms ion channels in both artificial and biological membranes. Accumulation of duramycin and coalescence of initially small channels into larger ones is considered to be responsible for the recorded behaviour and to final disruption of membranes.
Sheth
T R
TR
Department of Pharmacology, University of Cambridge, UK.
Henderson
R M
RM
Hladky
S B
SB
Cuthbert
A W
AW
D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism*; D008564:Membrane Potentials; D010455:Peptides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D007473:Ion Channels; D008051:Lipid Bilayers; D010455:Peptides; C040522:duramycin