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.