A quantitatively consistent model of nerve activity is given in terms of two main biochemical cycles narrowly interlocked: an acetylcholine cycle and a calcium cycle. The activity of both cycles is controlled among other things by the electric field and various allosteric effectors. As shown by digital simulations our model accounts for the basic properties of an action potential as described by the electrophysiologists. Thus the shape, time course, and behavior under voltage clamping conditions of both sodium and potassium permeability variations are adequately reproduced.We wish to report on a molecular model of the electrical activity of conducting membranes that takes into account the basic biophysical data well established in contemporary science.Since the Hodgkin-Huxley equations (1) for the squid axon membrane, many attempts at expressing electrical events in mathematical terms have been made. It should however be emphasized that unless a precise physical meaning is attributed to the various parameters or constants that inevitably appear in such formulations, their biological impact in terms of elementary molecular processes is rather weak.We believe that any model of nerve excitability should'take into account the following basic observations made over the years by generations of electrophysiologists: the threshold, the breakdown of membrane resistance, the graded response, the overshoot, the temporal dissociation of Na and K conductances, the spatial differentiation of the so-called Na and K channels, the different evolution of Na and K conductances under voltage-clamping conditions, the importance of Ca ions, and last but not least some fundamental concepts of general biochemistry and thermodynamics as applied to open systems far from equilibrium.Our phenomenological approach to the problem is basically inspired by the ionic hypothesis of the action potential as described by Hodgkin (2) while the molecular basis of the model is largely derived from the chemical theory of excitability proposed by Nachmansohn (3) more than two decades ago. An original addition is the description of what has been termed by one of us the enzymes of the impedance variation cycle (4-7). These are: acetylcholinesterase, choline acetylase, (Na + K)-ATPase, (Ca)-ATPase, an oxidoreductase. Our model takes into account the important observations that under voltage-clamping conditions, the change in Na conductance is transitory while the change in K conductance remains constant as long as the membrane is depolarized, thus suggesting a direct coupling between potassium permeability and membrane voltage. Moreover, we assume that the amount of calcium bound to the membrane is voltage-dependent. The more calcium bound to the membrane, the less permeable the membrane is to potassium ions. Together with electrophysiological evidence, pharmacological data are indicative of a spatial separation of both sodium and potassium channels, the gateways sometimes referred to as ionophores.In view of the peculiar evolution of the sodium co...