WATCHING SMALL MOLECULES MOVE - INTERROGATING IONIC CHANNELS USING NEUTRAL SOLUTES

Whether they are small enough to wriggle through the current-carrying part of an ionic channel or big enough to be kept outside and thus abl e to exert an osmotic stress on the channel space, polymers interact w ith channels in several instructive ways. The osmotic stress of exclud ed polymers allows one to measure the number of water molecules that c ome out of the channel in transitions between various ''open'' to ''cl osed'' states. The loss of osmotic activity, due to the partial or com pletely unrestricted admission of small polymers becomes a measure of the transfer probabilities of polymers from solution to small cavities : it provides an opportunity to study polymer conformation in a perfec tly sieved preparation. Current fluctuations due to the partial blocka ge by a transient polymer are convened into estimates of times of pass age and diffusion constants of polymers in channels. These estimates s how how a channel whose functional stares last for milliseconds is abl e to average over the interactions with polymers, interactions that la st only microseconds. One sees clearly that in this averaging, the mac romolecular channel is large enough to react like a macroscopic object to the chemical potentials of the species that modulate its activity.