Our studies have progressed by means of two strategies: 1) The structures of ionic channels can be interrogated by measuring their reaction to polymers of varied size 2) Sophisticated physical """"""""noise"""""""" analysis allows one to follow the very rapid kinetics of ionic channels in several different processes, such as the passage of neutral polymers through the channels or the formation of channels by drugs added to one side of a membrane Channels made from the peptide alamethicin have been observed while subjected to the osmotic action of differently sized neutral polymers. It is possible not only to see the degree of penetration of the polymers into the channel from their osmotic action but also to follow the kinetics of motion of small polymers through the ionic channel. These channels are sensitive to the identity of the phospholipids in the bilayer into which they are incorporated; in particular, there is a strong correlation between the probability of high-conductance states and the tendency of the phospholipid to form non-lamellar structures. The Hofmeister effect is shown to apply to transport properties of ionic channels. Chaotropic anions bind to roflamycoin channels for longer times, increase their conductance and induce cationic selectivity according to their position in Hofmeister series. Studies of the one-sided action of the drug amphotericin B (with the drug added only from one side of the bilayer) were conduced on cholesterol- and ergosterol-containing bilayers. As administered, drugs act predominantly from one side; furthermore, the differential toxicity of drugs appears to depend on the different sterol content of the tissue and the infectious agent; thus, this would appear to be the appropriate protocol for determining toxicity. Differences of drug action were in accord with expected discrimination under administration.
