Simulation of Use-Dependent Uptake of Ion Channel Blocking Agents by Excitable Membranes

Ion channel blocking agents have been difficult to characterize kinetically due to the use-and frequency-dependent nature of the observed channel blockade process. A model of ion channel blockade is presented which is based on single channel observations derived from patch clamp studies and a Hodgkin-Huxley-type channel gate that controls the diffusion path between ligand pool and the channel binding site. This model facilitates estimation and simulation of the pharmacodynamic properties of many local anesthetics and antiarrhythmic agents. The resulting model is easily implemented on small digital computers.