Desensitization of G protein-coupled receptors and the underlying mechanisms have been studied principally by biochemists. However, G protein-coupled receptors also couple to ion channels and the electrophysiologist can make an important contribution. Electrophysiological studies involving ion channel expression in Chinese hamster ovary (CHO) cells are made easier by the absence of native voltage-gated currents. CHO cells are derived from the ovary of the Chinese hamster, Cricetulus griseus. The small chromosome number of the nuclei of these cells have made CHO cell lines an ideal system for the study of genetic alterations in cultured mammalian cells. The chapter shows that the understanding of desensitization has resulted from the use of isolated heart cells as well as the reconstructed system in CHO cells and the whole cell, cell-attached, inside-out, conventional outside-out, and perforated outside-out configurations of the patch clamp technique.