Title: T-Tubule Function in Mammalian Cardiac Myocytes | Circulation Research
Headings: T-Tubule Function in Mammalian Cardiac Myocytes
T-Tubule Function in Mammalian Cardiac Myocytes
Abstract
Occurrence and Morphology of the T-Tubules
T-Tubule Development Is Labile
Proteins Present in the T-Tubule Membrane
Ca2+-Handling Proteins
Na+-Handling Proteins
K+-Handling Proteins
Anion-Handling Proteins
Second-Messenger Pathways
Interpretation of Immunohistochemical Data
Protein Colocalization Within, and With Proteins Adjacent to, the T-Tubules
Localization of Function
Cells Lacking T-Tubules
Diffusion Studies
Scanning Pipette
Detubulation
Functional Role
Electrical Properties of T-Tubules
Coupling of Ca 2+ Entry and Ca 2+ Release
Ca 2+ Efflux
Signal Transduction
Changes During Development and Disease
T-Tubule Development and Morphology in Hypertrophy and Failure
Changes in Protein Expression in Development, Hypertrophy, and Failure
Relevance of Changes in T-Tubule Structure and Protein Expression to Function
Conclusions and Unanswered Questions
Footnotes
References

Content: Although the diversity of estimates of the extent of the t-tubules within a species makes it impossible to determine whether there may be differences between species, it is tempting to speculate that the extent of the t-tubules varies between species depending on cell size (surface area/volume ratio) and heart rate if the t-tubules are necessary to produce synchronous Ca 2+ release throughout the cell (see Coupling of Ca 2+ Entry and Ca 2+ Release, later) and, hence, synchronous contraction. Although we are unaware of any differences related to cell size, the density of the t-tubular network is greater in the mouse, which has a resting heart rate of 300 to 400 bpm, than in the pig, which has a heart rate of <100 bpm. 1
T-Tubule Development Is Labile
Ventricular myocytes isolated from neonatal hearts show little evidence of t-tubule development, 4,18 and cells kept in culture for 6 days show a progressive decrease of t-tubule density. 19 T-tubule structure has also been reported to change in myocytes from failing hearts (see T-Tubule Development and Morphology in Hypertrophy and Failure). However, the mechanisms underlying the expression and maintenance of the t-tubules are not clear. Once formed, the ability of the tubular system to maintain its remarkable degree of structure despite the forces exerted during the normal contraction cycle may be due to the presence of a “scaffold” of focal adhesion molecules, membrane-associated proteins, and basal lamina proteins. 20
Proteins Present in the T-Tubule Membrane
The function of the t-tubules depends not only on their structure but also on the proteins within, and adjacent to, the t-tubule membrane. Immunohistochemical techniques have been widely used to investigate the location of proteins within cardiac ventricular myocytes. Such studies have shown marked variations in the distribution of membrane proteins, although a distinction needs to be drawn between the fraction of a particular type of protein located at the t-tubule and whether this is greater than the fraction of the total cell membrane located within the t-tubules, ie, whether protein density is higher (concentrated) at the t-tubule. This is discussed further in Interpretation of Immunohistochemical Data and in Conclusions and Unanswered Questions.