THE ROLE OF TRANSVERSE TUBULES IN EXCITATION CONTRACTION COUPLING IN STRIATED MUSCLES *

The use of glutaraldehyde as a fixative for electron microscopy recently has resulted in better images of certain cellular structures than could be obtained with earlier fixatives. This new fixative is particularly useful with tubular structures, such as are found in the internal membrane systems of striated muscle cells, and many previously outstanding questions on the arrangement of these membranes have now been answered. Although there is wide variation in the form of these structures in different kinds of muscle cells, certain morphological features common to most if not all striated muscles have now become apparent. For example, it has become clear that two separate membrane systems are present in each cell type. One of these, the sarcoplasmic reticulum (SR) is truly intracellular. It has never been found to be continuous with the cell surface, although a direct connection of the SR to the nuclear membrane has been seen. In this respect, the SR is homologous with the endoplasmic reticulum of other types of cells. The second membrane system in muscle cells is a continuation of the cell surface into the interior of the cell, and has been called the transverse tubular system or T-system. Close association, but not direct membrane continuity of these two membrane systems with each other, is commonly observed. The degree of development and the form of the SR and the transverse tubules varies greatly in different muscles. Usually these two membrane systems are regularly disposed with respect to the striations of the myofibrils. Local structural differentiations of the SR repeat in phase with the myofibrillar striation pattern, so that an exact spatial relationship between elements of the SR and the contractile myofilaments is maintained throughout the muscle fiber. This has suggested to many workers that there may be a close functional relationship between the SR and the myofibrils (e.g., Porter & Palade, 1957; A. F. Huxley & Taylor, 1958; Ruska et al., 195s; A. F. Huxley, 1959; Peachey &Porter, 1959). The most attractive idea that has been presented is that the SR somehow controls the contractile state of the myofibrils by accumulating and releasing calcium ions to the sarcoplasm at the appropriate moments. Microinjection experiments have shown the elevation of internal calcium in cut segments of frog muscle fibers is sufficient to cause contraction (Kamada & Kinosita, 1943; Heilbrunn & Wiercinski, 1947). The continuity of the transverse tubules across the diameter of the muscle fiber would seem to suit them for a role in conveying the triggering of contraction from the cell surface through the entire volume of the muscle fiber, a process that has been called excitation-contraction coupling. There now seems to be a considerable amount of morphological evidence for such a scheme, and also some physiological evidence on how it might work. It will be the purpose of this paper to review the present state of our information in this area. The emphasis will be on morphology, where our information is most complete. The electron micrographs used for illustration have not been published before.