ABSTRACT
There are ~23,000 human protein-coding genes. One third of them encode membrane proteins including ion channels, receptors, transporters, and exchangers.1,2 To understand the physiological function of individual genes, the development of speci—c tools targeting the gene of interest is essential. The technology by gene modi-—cation, such as antisense oligonucleotides, small interfering RNA (siRNA), gene knockout, or transgenic animals, has provided useful approaches to reveal individual gene function; however, some limitations of these techniques are inevitable. Among them, the knockdown of protein expression takes time (at least days) and will likely cause compensatory changes that obscure the interpretation of the research —ndings. The study of cell surface receptors and ion channels has bene—ted greatly from the use of small molecule blockers and activators, which cause acute modulation of the protein function, allowing direct comparison of the sample before and after the drug treatment. This often provides a clear answer as to whether the target protein is involved in the physiological process being studied without a concern of the compensatory effect.
