Measurements are performed with a device consisting of an ISFET pH-sensor in the middle of a Ag/AgCl electrode, on top of which a microporous composite membrane is deposited. A sudden change of the salt concentration in the bathing electrolyte causes a transient change in the electrical potential of these sensors when measured vs. a reference electrode in the bathing electrolyte. The potential transient is modulated by adsorption of protein to the membrane. To explain the measured transients, a model is presented for the measuring device describing the ion transport by the Nernst-Planck and Poisson equations, incorporating the different proton-dissociation reactions occurring in the system, and the sensor responses to their potential determining ions (the proton or the Cl- ion). A finite-difference solution method is presented to solve the resulting differential equations. Measurements are performed before and after the adsorption of the model protein lysozyme to the membrane. Analysis of the measurement results indicates that the measured potential transient is caused by a change of the Donnan potential of the membrane, followed by a compensating change in the concentration of the potential determining ion. It is proven that no diffusion potential is generated, In addition, it is shown that an interlayer of electrolyte between membrane and measuring electrode will not influence the measured response. The potential transients measured by the ISFET have a larger amplitude and a longer duration than the Ag/AgCl-measured transients. An analysis shows that this is caused by the buffering action of the proton-dissociating membrane groups. The longer duration results from the release of a large amount of protons from binding to fixed groups, while chloride ions are not bound. The larger amplitude can be explained by refining the Donnan model to account for the inhomogeneous charge distribution in the membrane. The proton-dissociating groups reside at the surface of the polystyrene beads, at which place the potential change on an ion step is larger than the average in the membrane pore solution. This surface-potential change can be measured by the pH-sensitive ISFET because a proton release occurs from the surface-bound groups into the membrane pores, changing the pore pH.