A relatively large group of compounds, which includes local anesthetics, antiarrhythmics, and anticonvulsants induce voltage- and/or frequency-dependent block of sodium and other ion channels. Current block increases as the stimulus voltage and frequency of depolarization is increased. These voltage- and frequency-dependent blocking properties have been recognized for over 40 yr (Weidmann, 1955), and the voltage- and use-dependent properties of a wide range of molecules have been described in detail.
A characteristic set of features describes local anesthetic block, but the prevalence (or presence) of any one of these characteristics varies with drug structure and physical properties (Butterworth and Strichartz, 1990; Hille, 1992), which in turn affects the qualitative characteristics of current block. In quiescent cells with a very negative resting potential, even relatively high local anesthetic concentrations have little effect on electrical activity. However, when depolarizing pulses arrive at high frequency, the peak sodium...
