Studies on ionic transport induced by carriers and channels are proposed to further understanding of the molecular factors underlying ion permeation, voltage gating and anomalous rectification in membranes of excitable cells, such as nerve, muscle and heart. Know variations in the structure of ion selective carriers will be related to changes of the electrical properties they induce in membranes. Emphasis will be placed on those features of permeation that are common to both carriers and channels, such as loading and unloading of ions, and the rate constants for their kinetics will be evaluated. A class of calcium-carrier antibiotics will also be characterized, and theoretical studies will be extended to encompass the effects of diffusion-coupled ion-carrier homogeneous reactions. In addition, ion permeation in channels will be investigated theoretically and experimentally. Conventional descriptions of the fluxes will be generalized to allow for multiple occupancy and ion interaction, such as are frequently invoked to account for deviations from the "independence principle" observed in nerve and other excitable cells. The results of the theory will be tested by studying the conductivity properties of the single pore of alamethicin. A model for "anomalous rectification", where ion binding is required to form voltage gateable channels, is discussed. Ion binding by the voltage gated alamethicin channel is examined, and experiments are proposed to test whether the expectations of the model can be reproduced by alamethicin doped membranes.
NIH ExPorter
NIH ExPorter