Perchlorate as a couplon agonist. (A) The EC coupling transfer function; relationship between amount of voltage sensor charge displaced and peak Ca²⁺ release flux (measured in voltage-clamped cell of the frog semitendinosus muscle). Perchlorate linearizes the relationship in a dose-dependent manner. (B) An allosteric model, which uses the MWC formalism to describe the activation of release channel opening (represented by the transition from states C_j to O_j) by the operation of four voltage sensors (circles); upon membrane depolarization these move to the activating position (represented as +) in a sequence progressing from left to right. The model reproduces many features of Ca²⁺ release activation, including the effects of perchlorate. This anion is assumed to increase the single parameter f, which embodies the activating effect of each moving voltage sensor. Changes in the transfer function (represented in C) and charge displacement then ensue. Panels are modified from Ríos et al. (1993).