Macroscopic Currents

Once an appropriate mechanism has been chosen, and values for its rate constants have been estimated, then programs exist to calculate the time course of macroscopic currents under any specified conditions (e.g., SCALCS from http://www.ucl.ac.uk/Pharmacology/dc. html). Thus it can be seen whether the fitted mechanism is capable of predicting the time course of synaptic currents. The resolution of single-channel experiments is so much greater than that for measurements of macroscopic currents that it is not possible to go the other way. Figure 11.17 shows the calculated response to a 0.2-ms pulse of 1 mM ACh for both wild-type and the eL221F mutant. Despite the complexity of the mechanism (the curve has six exponential components), the decay phase is very close to a single exponential curve in both cases. This calculation predicts that the mutation will cause a sevenfold slowing of the decay of the synaptic current, much as observed for miniature end-plate currents measured on a biopsied muscle fiber from a patient with the eL221F mutation (102).

The relationship between single-channel currents and macroscopic currents has been considered both experimentally and theoretically by Wyllie et al. (104), who give the general relationship that relates the two sorts of measurement.

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