Properties a N D Function of Proteins in Excitable Membranes : an Integral Model of Nerve

As was stated by Hill 15 years ago, the strong heat production and absorption that coincides with electrical activity leaves us with no alternative to the assumption that the changes of ion permeability in excitable membranes are associated with chemical reactions. These and other experimental facts are incompatible with the assumption that electrical activity is a simple electrodiffusion process, as is still maintained by some investigators. According to Cole,a the Planck model does not apply to biological membranes. A chemical theory of the events that take place in excitable membranes during electrical activity has been elaborated over the last three decades. The theory is based on the analyses of the properties and functions of the proteins and enzymes that process AcCh.:" Since 1937, the use of the electric organs of fish has been instrumental in these studies. Their extraordinarily high specialization in bioelectrogenesis offers a uniquely favorable material for the protein chemist. As a result of the biochemical approach to the function of excitable membranes, it became apparent that AcCh is not a neurohumoral transmitter, as has been assumed, but is released and acts within the membrane. It is the signal that on excitation starts a series of reactions that lead to increased permeability (FIGURE 1) . This series of reactions leads to the amplification of the signal. Many thousands of ions (about 20,000 to 30,000) cross the membrane in each direction per molecule of AcCh released. Two brief comments may be appropriate. The enzyme is uniformly distributed along the whole excitable membrane, in the conducting as well as in the junctional parts (FIGURE 2). The concentrations may differ in different types of excitable membranes; they are remarkably high in the excitable membrane of electroplax, in which about 10" molecules of enzyme are present; the number of receptor molecules is of the same order of magnitude. The theory is not based upon the presence and the high concentrations of these proteins, however, but upon the many functional relationships between enzyme and receptor proteins and