Voltage clamp simulation.

The voltage clamp experiment on the squid giant axon is successful because of the special characteristics of the preparation: cylindrical shape, large diameter, and so on. The method is much more difficult to apply to small cells and to networks of cells because voltage gradients and unwanted stray impedances are not readily eliminated. Simulation of the voltage clamp experiment is proposed as a method for determining when these factors and the characteristics of the clamp electronics affect the experimental results, for evaluating experimental techniques for improving the quality of the clamp, and as a possible method of learning something about the membrane when no experimental improvement is feasible. The numerical methods for including one spatial variable in the analysis are reviewed briefly. Several examples of voltage clamp simulations are discussed: double sucrose gap clamp of axons, clamp of the giant synapse, single sucrose gap clamp of cardiac muscle bundles, point clamp of the end of a fiber bundle, and the steady-state three-microelectrode clamp of a cable with nonlinear membrane. The results indicate that the quality of a clamp cannot be evaluated from the voltage and current records as commonly measured.