NYSTATIN-INDUCED, MYCOHEPTIN-INDUCED AND LEVORIN-INDUCED CONDUCTANCE IN THE MEMBRANE OF FROG SKELETAL-MUSCLE FIBERS

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 g(A infinity) and efflux rate constants K-A 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 Ig of antibiotic concentration in our experiments had slope values which were much lower than these 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 conduc tance 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.