Nystatin-, mycoheptin- and levorin-induced conductance in the membrane of frog skeletal muscle fibres.
The effects of the polyene antibiotics nystatin (2 x 10(-5)-10(-4) mol/l), mycoheptin (1.3 x 10(-6)-10(-5) mol/l) and levorin (10(-8)-5 x 10(-5) mol/l) on isolated frog skeletal muscle fibres and whole sartorius muscles of the frog have been investigated. Cation conductance was measured under current clamp conditions using a double sucrose-gap technique. Cation effluxes were studied by means of flame emission photometry. All three antibiotics increased the cation conductance and efflux rates; however, differences between the polyenes were found in the steady state values of induced cation transport at a given concentration. The values of both induced conductance gA infinity and efflux rate constants KA formed the following sequence: levorin > mycoheptin > nystatin, demonstrating a correlation with the order of antifungal activities. The dose-response curves of lg polyene-induced cation transport against lg of antibiotic concentration in our experiments had slope values which were much lower than those in bilayers: 1.7 and 1.3 for nystatin and mycoheptin, respectively, whereas the aromatic heptaene levorin had an even smaller concentration dependence. The decline in the equilibrium conductance caused by nystatin- and mycoheptin removal was very fast (during the first minute tau = 0.74 and 2.39 min, respectively). In contrast, levorin-induced conductance was irreversible. It is proposed that the processes which limit the rate of channel formation are different in biological and model membranes.
Shvinka
N E
NE
Institute of Cytology, Russian Academy of Sciences, St. Petersburg.
Caffier
G
G
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002174:Candicidin / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008051:Lipid Bilayers; D018485:Muscle Fibers, Skeletal / Q000187:drug effects*; D009431:Neural Conduction / Q000187:drug effects; D009761:Nystatin / Q000494:pharmacology*; D011090:Polyenes / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011896:Rana temporaria; D012413:Rubidium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D000935:Antifungal Agents; D008051:Lipid Bilayers; D011090:Polyenes; D009761:Nystatin; D002174:Candicidin; D012964:Sodium; C008567:mycoheptin; D012413:Rubidium; D011188:Potassium