Title: Cardiac T-Tubule Microanatomy and Function | Physiological Reviews
Headings: Cardiac T-Tubule Microanatomy and Function
Cardiac T-Tubule Microanatomy and Function
Abstract
I. INTRODUCTION
II. CARDIAC T-TUBULE STRUCTURE
A. History of T-Tubule Structure-Related Research
B. Gross Morphology and Geometry
C. Membrane Ultrastructure and Microdomains
1. cBIN1 microfolds: microdomains supporting LTCC-RyR dyads
2. Caveoli (caveolae): β-AR/LTCC signaling hubs
3. Ankyrin B microdomains: NCX/NKA/InsP 3 macromolecular complex
D. Peri-Membrane Cytoskeleton Scaffolds at Cardiac T-Tubules
1. Actin filaments, tropomyosin, and N-WASP
2. Costamere complex and t-tubule membrane-associated scaffolds
3. Myofilament structural proteins
E. Variation in Cardiac T-Tubule Geometry
III. TRANSMEMBRANE PROTEINS AT CARDIAC T-TUBULES
A. Ion Handling Proteins (Channels/Transporters/Pumps)
1. Ca 2+ handling proteins
2. Na + handling proteins
3. K + handling proteins
B. Signaling Molecules at Cardiac T-Tubules
IV. FUNCTION OF CARDIAC T-TUBULES
A. Dyad and EC Coupling
1. LTCC trafficking and clustering to dyads through BIN1
2. RyR recruitment to dyads through BIN1
3. Junctophilin-2 in t-tubule-jSR junctional membrane complex formation
B. Ion Diffusion and Membrane Excitability
C. Other Microdomain-Related Functions
V. LIFE CYCLE OF CARDIAC T-TUBULES
A. Membrane Biogenesis, Maintenance, and Turnover
B. Ion Channel Trafficking and Half-Life
VI. ALTERATION OF T-TUBULE STRUCTURE AND FUNCTION IN HEART FAILURE
VII. CONCLUSIONS
GRANTS
DISCLOSURES
Acknowledgments

Content: Retzius first proposed the existence of t-tubules over 130 years ago, in 1881, when exploring the quick inward spread of action potentials penetrating into muscle cells (see the 1967 Croonian lecture by Huxley) ( 95 ). The first visual evidence of tubular structures around myofilament was in 1897 by light microscopy in Nystrom's study ( 95 ), when he injected mammalian heart muscle with India ink to track extracellular space. Later, in 1924, Tiegs visualized Z-lines as a spiral structures where inward spread of action potential occurs ( 95 ). However, it was not until the 1950s that Huxley and his peers reported, in various muscle cells, the structure for inward spread as tubular membrane structures at the I band (which spans the Z-line) ( 96 ). The primary element of cardiac t-tubules is transverse to the long axis of myocytes and occurs periodically at sarcomeric z-discs of myofilament ( 126 ). By using transmission electron microscopy (TEM) imaging methods in 1957, Lindner ( 126) identified that these transverse cardiac t-tubules are open to extracellular space. The longitudinal axial component of t-tubules was identified later in 1970s ( 201 ), adding the complexity of the t-tubule system. The 1960s and 1970s was a period of improved TEM and sample preparation technology which led to prolific t-tubule morphology research ( 60, 62, 153, 190, 191, 201 ), reveal