NMDA Receptor Pharmacology and Analysis of Patch-Clamp Recordings

There are two approaches to evaluation of the effects of drugs on steady-state ligand-gated receptor function: (1 ) concentration-response curves derived from whole-cell recordings and (2 ) analysis of single-channel recordings. Whole-cell currents are the average response of a large population of channels, whereas single-channel recordings document the gating behavior of a single protein. Analysis of single-channel recordings details the effects of modulators and agonists on channel kinetics at the molecular level. Whole-cell concentration-response analysis is a standardized protocol for classification and interpretation of a mechanism that permits quantitative comparisons with other modulators. Quantitation of charge at the single-channel level can be used as a basis for comparison with whole-cell concentration-response curves. This procedure allows the investigator to compare the effects of a variety of drugs at the molecular level using a well-established set of tools developed for analysis of macroscopic responses.