Several important physiological processes such as plasticity, memory, cell death, and rhythmic firing involve the N-methyl-D-aspartate (NMDA)-type of glutamatergic receptor. Nicotinic acetylcholine receptors (AChR), recently demonstrated in the central nervous system (CNS), are also of great interest. We have used several ligands to study the physiology and pharmacology of the agonist recognition sites of these receptors and kinetic properties of associated ion channels using whole-cell, cell-attached or outside-out variants of the patch-clamp technique. Enzymatically dissociated frog interosseal muscles were used to study peripheral AChRs, and tissue cultured or acutely dissociated hippocampal neurons and retinal ganglion cells (RGCs) for CNS receptors. For reproducible and fast solution changes when recording in the whole-cell configuration, we modified the "U"-shaped tube system to obtain different outputs from the same outflow port. We used fluorescent rhodamine-labeled latex microspheres to identify RGCs. Our studies provide important information regarding the molecular mechanisms of several clinically used agents. Additionally, similar actions of noncompetitive agents on the ion channels of the nicotinic ACh and NMDA receptors support the concept of a receptor ion channel superfamily.