Membrane permeability and receptor function.

This paper presents a model of receptor function for receptors that mediate selective increases in ionic permeabilities (e.g. receptors that are sensitive to acetylcholine and gamma-aminobutyric acid). The model distinguishes itself from previous models by the qualitative and quantitative application of current biophysical approaches to ion permeation. Explicit consideration of receptor-controlled permeation sites and membrane permeability results in a specific and testable theory into which complex receptor phenomena can easily be incorporated.Examination of agonist concentration-conductance data from a well-studied GABAnergic receptor allows invalidation of a standard assumption for determining kinetic constants of agonist-receptor interactions. Specifically, calculations are presented which indicate that the size of an individual receptor (elementary) conductance event can vary with agonist concentration. The following section develops the expressions relating agonist concentration to total membrane conductance for possible receptor models which incorporate variations in the amplitude of elementary conductance events.In the case of desensitization, the “inactivated” receptor is suggested to result from occupation and inactivation, not at the agonist-binding (activation) site of the receptor, but at the ionophore. The ionophore occupation model provides a parsimonious explanation of different types of desensitization. In addition, incorporation of this model into the cyclic reaction model of Katz &; Thesleff (1957) provides increased specification for the cyclic model and results in new experimental predictions.