Gramicidin forms multi-state rectifying channels

Gramicidin A is a pentadecapeptide of alternating L and D amino acids. In membranes it forms cation conductive channels(2) of molecular dimensions(3,4) that in many respects resemble(2-7) the channels of excitable cells(8,9). For this reason, and also because its structure is well established(1,10,11), the gramicidin channel is regarded as a useful model of ion channels in cell membranes. Although the properties of the gramicidin channel have been studied extensively(12), it has generally been described as having a single state associated with a sharply defined conductance that remains unaltered during the lifetime of the 13 channel We report here that, in fact, gramicidin A can assume other, less conductive 'miniature' (mini) states evidenced by our observations of spontaneous transitions in the conductance of single open channels and the observation of a significant number of weakly conducting channels. Current-voltage (I-V) relationships for different channel states differ significantly and, for minis, are often asymmetrical. Our results indicate that the gramicidin channel has a wide variety of stable conformational states that give rise to channels with different electrical properties. Because transitions between states occur relatively infrequently, these conformational states must be separated by relatively large energies of interconversion. Similar transitions, poised by the electric field or an agonist molecule, may underlie the function of gated channels in cell membranes.