Since the work of Ringer (1883), it has been clear that cells modify their behavior according to the ionic composition of the external medium. Thus, Ringer showed that the excised frog heart requires sodium, potassium, and calcium to continue beating. On this basis, Berstein (1902) proposed a mechanism for the generation of the resting potential. He suggested that the resting membrane of a nerve or a muscle is only permeant to potassium ions. He further proposed that during activity the membrane permeability became transiently nonselective. Thus, we have known for a long time that membranes are permeable to ions. Since a lipid bilayer presents an enormous energy barrier to the movement of small ions like potassium (60 kcal/mol), a class of membrane protein has evolved to catalyze ion movement. Ion channels can be defined as integral membrane proteins spanning the bilayer and able to connect the internal with the external medium of the cell.