One of the basic tenets of experimental science has been the search for techniques that give relevant information from intact systems while causing minimal effects. This concept is particularly important in the physiological branch of the biological sciences. In general, reductionist methods assume that the net behavior of a system is the result of the summation of individual parameters, an assumption that is not always true in the biological sciences. On the other hand, in electrophysiology, reductionist methods have been successful, especially using voltage and current patch-clamp techniques. These, however, have practical limitations in that in general they require special processing of cells and tissues for their application. The effects of special processing become more notable with the need for having “clean” surfaces for the formation of tight seal patches. Although voltage- and current-clamp techniques with tight seals have given good information on the biophysical characteristics of ionic currents (and channels), such information from intact or in situ systems is more difficult, because these are minimally altered preparations. Information obtained with tight-patch techniques is also limited by the changes caused in the internal environment of cells (whole-cell configuration) or isolation from external effects (i.e., isolation of the patch under the cell-attached configuration).