A macromolecular approach to excitation phenomena: mechanical and thermal changes in nerve during excitation.

(1) Nerve fibers and cells were shown to swell when they develop action potentials. Both in the squid giant axon and in the garfish olfactory nerve, the peak of swelling coincides with the peak of the action potential recorded from the site of mechanical recording. Substitution of univalent cations for the bivalent cations (Ca) bound to multi-anion sites in the membrane macromolecules is considered to be at the base of the phenomenon of swelling. (2) Measurements of heat production by the garfish olfactory nerve indicate that the rate of temperature rise is maximal at the peak of the action potential. Since heat production lasts for the entire depolarizing phase of the action potential, the "condenser theory" of heat production is abandoned. Again, substitution of the bound bivalent cations in the membrane macromolecules with univalent cations is regarded as the origin of nerve heat. (3) The two stable states of the nerve membrane, which are readily demonstrable in TEA-treated or internally perfused squid giant axons, are shown to represent bivalent cation-rich and univalent cation-rich states of the nerve membrane. (4) A physicochemical theory is described that explains macromolecular transitions between two stable states. The mechanism of nerve excitation is explained on a physicochemical basis. (5) The importance of the role played by water molecules in the process of nerve excitation is emphasized.