A perfect confluence of physiology and morphology: discovery of the transverse tubular system and inward spread of activation in skeletal muscle

Abstract

By early 1954, there existed a plausible model of muscle contraction called the sliding filament model. In addition, the nature of muscle excitation was understood. Surprisingly, the link between the membrane excitation and contraction was entirely unknown. This dilemma has been called the time-distance paradox. The path to discovery of the missing link between excitation and contraction was a rocky one involving the simultaneous but independent development of physiological and morphological studies. From the viewpoint of physiology, significant events included the most thrilling moment of a scientific life, confirmation of a hypothesis that was wrong, a major surprise and shock, a result not expected from evolutionary relationships, and disappointment and confusion before clarity. From the viewpoint of morphology, there was the exciting beginning and rapid development of biological electron microscopy, heroic experiments, the importance of sample preparative procedures, and discovery of clues from the old light microscopic literature. However, it was the confluence of physiology and morphology that brought clarity and a major advance in understanding, leading to the discovery of the transverse tubular system and inward spread of activation in skeletal muscle.