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: TRANSMEMBRANE PROTEINS AT CARDIAC T-TUBULES
A. Ion Handling Proteins (Channels/Transporters/Pumps)
B. Signaling Molecules at Cardiac T-Tubules
IV. FUNCTION OF CARDIAC T-TUBULES
A. Dyad and EC Coupling
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
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Abstract
Unique to striated muscle cells, transverse tubules (t-tubules) are membrane organelles that consist of sarcolemma penetrating into the myocyte interior, forming a highly branched and interconnected network. Mature t-tubule networks are found in mammalian ventricular cardiomyocytes, with the transverse components of t-tubules occurring near sarcomeric z-discs. Cardiac t-tubules contain membrane microdomains enriched with ion channels and signaling molecules. The microdomains serve as key signaling hubs in regulation of cardiomyocyte function. Dyad microdomains formed at the junctional contact between t-tubule membrane and neighboring sarcoplasmic reticulum are critical in calcium signaling and excitation-contraction coupling necessary for beat-to-beat heart contraction. In this review, we provide an overview of the current knowledge in gross morphology and structure, membrane and protein composition, and function of the cardiac t-tubule network. We also review in detail current knowledge on the formation of functional membrane subdomains within t-tubules, with a particular focus on the cardiac dyad microdomain.