Gramicidin - Pharmacological Effect

Pharmacological Effect

Gramicidin's bactericidal activity is a result of increasing the permeability of the bacterial cell membrane, allowing inorganic monovalent cations (e.g. Na+) to travel through unrestricted and thereby destroying the ion gradient between the cytoplasm and the extracellular environment.

That gramicidin D functions as a channel was demonstrated by Hladky and Haydon, who investigated the unit conductance channel. In general, gramicidin channels are ideally selective for monovalent cations and the single-channel conductances for the alkali cations are ranked in the same order as the aqueous mobilities of these ions. Divalent cations like Ca2+ block the channel by binding near its mouth so that it is essentially impermeable to divalent cations and also excludes anions. Cl− in particular is excluded from the channel because its hydration shell is thermodynamically stronger than that of most monovalent cations. The channel is permeable to most monovalent cations, which move through the channel in single file. The channel is filled with about six water molecules, almost all of which must be displaced when an ion is transported. Thus, ions moving through the gramicidin pore carry along a single file of water molecules. Such a flux of ion and water molecules is known as flux coupling. In the presence of a second type of permeable ion, the two ions couple their flux as well. Like valinomycin and nonactin, the gramicidin channel is selective for potassium over sodium but only slightly so. It has a permeability ratio of 2.9. Though it is impermeable to anions, there are conditions under which some anion permeation may be observed. Its ability to bind and transport cations is due to the presence of cation-binding sites, one strong and the other weak, in the channel.