Analysis of drug action at single-channel level

Many drugs interact directly with ion channel proteins to alter gating and permeation functions. Single-channel recording affords resolution of drug-induced functional changes in channel behavior at the molecular level. Drug and toxin molecules that block ion channels are useful probes of channel mechanisms because blocking sites are often coupled to other pharmacologically relevant binding sites. Simple kinetic schemes describing fast block, slow block, and binding competition between two blocking molecules provide useful models of drug-induced blocking processes. From a careful perspective, a single channel is best approached as the analog of a purified enzyme preparation in the hands of an enzymologist. The confidence gained by knowing that one is viewing a single subtype must be weighed against the possibility that the channel could have been altered in the process of patch isolation or bilayer reconstitution. As in all kinetic studies, a curve fit to a two-state scheme is contingent on the possibility that a more complex multi-state system can masquerade as the simple cartoon one would like to put forward.