Voltage-gated anion channels are present in almost every living cell and ha
ve many physiological functions. Recently, a novel gene family encoding vol
tage-gated chloride channels, the ClC family, was identified. The knowledge
of primary amino acid sequences has allowed for the study of these anion c
hannels in heterologous expression systems and made possible the combinatio
n of site-directed mutagenesis and high-resolution electrophysiological mea
surements as a means of gaining insights into the molecular basis of channe
l function. This review focuses on one particular aspect of chloride channe
l function, the selective transport of anions through biological membranes.
I will describe recent experiments using a combination of cellular electro
physiology, molecular genetics, and recombinant DNA technology to study the
molecular basis of ion permeation and selection in ClC-type chloride chann
els. These novel tools have provided new insights into basic mechanisms und
erlying the function of these biologically important channels.