The use of the driving function in the analysis of endplate current kinetics

The time course of transmitter release at the neuromuscular junction is non-instantaneous and is more prolonged for nerve-evoked endplate currents (EPCs) than for miniature endplate currents (MEPCs). This creates difficulties in the interpretation of the effects of ion channel blocking drugs which greatly increase the rate of EPC decay, resulting in a substantial number of channels being blocked during the EPC rising phase. Apparent changes in peak current and in the EPC/MEPC peak current ratio can be erroneously interpreted as receptor block or effects on quantal content. A method is described for a more precise assessment of receptor block or quantal content in the presence of ion channel block, by calculation of the EPC driving function. The driving function is a measure of the rate of opening of the ion channels in response to transmitter release, and is independent of ion channel block effects. Simulated EPCs with the same decay rate can be created from the driving functions of EPCs in control and in the presence of the drug. The peak current of such EPCs can be compared to reveal any additional receptor block or quantal content effects independent of a drug's ion channel blocking effects.