Automatic control of potential and agonist-induced current across the endplate membrane by drug electrophoresis

Two techniques are described that are designed to elicit long and constant postsynaptic depolarizations or agonist-induced currents by the electrophoretic application of agonists to endplate membranes. In the first technique, which can be described as a "pharmacologic voltage clamp," the current flowing through the agonist pipette is controlled by the potential across the endplate membrane. Sustained depolarizations of constant amplitude can be obtained in this manner, while the agonist current needed to produce and maintain the response is recorded. The second technique uses a signal proportional to the current flowing across a voltage-clamped endplate membrane to control the delivery of agonist. This allows control of the intensity of the agonist-induced current. The possible application of these techniques in studying receptor desensitization and obtaining samples of post-synaptic current noise for spectral analysis is discussed.