ANALYSIS OF THE ALAMETHICIN INDUCED SINGLE CHANNEL CONDUCTANCE FLUCTUATIONS IN LIPID BILAYERS AS A BIRTH AND DEATH PROCESS

Conductance fluctuations induced by low concentrations of alamethicin in lipid bilayer membranes have been examined using a novel computer-aided analysis. It is shown that the system conforms closely to a birth and death process. The complete set of the rate parameters governing the steady-state distribution is derived and it is shown that these parameters can be used to reconstruct exactly the experimental relative frequency distribution. The transition rates of inclusion or exclusion of one molecule of alamethicin are estimated on a statistical basis and are modelled on the same basis as electrochemical rate constants. Hence it is shown that the electrochemical Gibbs energy of the conductance states varies quadratically with the state number; the Gibbs energy of activation of both the inclusion (birth) or exclusion (death) processes is related linearly to the Gibbs energy differences between the states. A detailed model based on the nucleation of a two-dimensional pore accounts for these observations. This model require two energy parameters, the "edge" and "bulk" energies of the pore. Experiments have been performed using a patch-clamp technique and a membrane a few micrometers in diameter where only one pore is opened at the time. A birth and death process interprets the experimental results quite closely and the kinetics of opening and closing of the pore can be evaluated.