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- W1770594995 abstract "For excitable membranes, use and frequency dependence represent a progressive incorporation of drug into gated ion channels with repetitive stimulation. In contrast to receptors where access to ligand is continuous in time, we define guarded receptors, such as gated ion channels, as receptors whose access to the ligand pool is transient and controlled by the channel-gating process. During repetitive stimulation, the fraction of ligand-bound channels (ion channel blockade) follows an exponential time course, determined by the interstimulus interval, channel-gating processes, drug concentration, and the forward and reverse rate coefficients characteristic of the binding process. Based on a first order model of ligand-receptor binding, we derive a characterization of ion channel blockade via a single diffusion path under conditions of repetitive phasic stimulation. Extension to multiple diffusion paths and multiple drugs leads to a more complex scheme, but these generalizations are straightforward. For the case of one diffusion path, we derive the steady state level of channel blockade for guarded receptors as a function of stimulus rate and develop a data analysis strategy suitable for characterizing ion channel-blocking agents such as local anesthetics and antiarrhythmic drugs. We show that as receptor access time increases, the transient and steady state properties of guarded receptors become equivalent to those derived from the standard continuous access ligand-receptor model. The analysis tools presented simplify the quantitative description of the functional properties of many ion channel blockers and appear to have general applicability to characterization of periodically accessible receptors." @default.
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- W1770594995 date "1985-10-01" @default.
- W1770594995 modified "2023-09-23" @default.
- W1770594995 title "Phasic ion channel blockade. A kinetic model and parameter estimation procedure." @default.
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