Evolutionary History of Voltage-Gated Sodium Channels.

Every cell within living organisms actively maintains an intracellular Na+ concentration that is 10-12 times lower than the extracellular concentration. The cells then utilize this transmembrane Na+ concentration gradient as a driving force to produce electrical signals, sometimes in the form of action potentials. The protein family comprising voltage-gated sodium channels (NaVs) is essential for such signaling and enables cells to change their status in a regenerative manner and to rapidly communicate with one another. NaVs were first predicted in squid and were later identified through molecular biology in the electric eel. Since then, these proteins have been discovered in organisms ranging from bacteria to humans. Recent research has succeeded in decoding the amino acid sequences of a wide variety of NaV family members, as well as the three-dimensional structures of some. These studies and others have uncovered several of the major steps in the functional and structural transition of NaV proteins that has occurred along the course of the evolutionary history of organisms. Here we present an overview of the molecular evolutionary innovations that established present-day NaV α subunits and discuss their contribution to the evolutionary changes in animal bodies.

On the Natural and Unnatural History of the Voltage-Gated Na(+) Channel.

This review glances at the voltage-gated sodium (Na(+)) channel (NaV) from the skewed perspective of natural history and the history of ideas. Beginning with the earliest natural philosophers, the objective of biological science and physiology was to understand the basis of life and discover its intimate secrets. The idea that the living state of matter differs from inanimate matter by an incorporeal spirit or mystical force was central to vitalism, a doctrine based on ancient beliefs that persisted until the last century. Experimental electrophysiology played a major role in the abandonment of vitalism by elucidating physiochemical mechanisms that explained the electrical excitability of muscle and nerve. Indeed, as a principal biomolecule underlying membrane excitability, the NaV channel may be considered as the physical analog or surrogate for the vital spirit once presumed to animate higher forms of life. NaV also epitomizes the "other secret of life" and functions as a quantal transistor element of biological intelligence. Subplots of this incredible but true story run the gamut from electric fish to electromagnetism, invention of the battery, venomous animals, neurotoxins, channelopathies, arrhythmia, anesthesia, astrobiology, etc.