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: Estimates of the percentage of the ventricular myocyte volume occupied by the t-tubules varies from 3.6% in rat myocytes 2 to 0.8% in mouse myocytes, 7 although this variation probably reflects methodological rather than species differences because there appears to be no clear relationship between species and estimates of percentage cell volume occupied by the t-tubules. Similarly, estimates of the percentage of cell membrane located in the t-tubules vary from 64% (calculated in Bers 11 from data in Soeller and Cannell 2) to 21%, 15 with no apparent species differences. The t-tubules of cardiac muscle have a mean diameter of ≈200 to 300 nm, 13 although within a single rat ventricular myocyte, the diameter of individual tubules can vary from 20 to 450 nm, but with more than half the t-tubules having diameters between 180 and 280 nm. 2 One consequence of this network of narrow tubules is that a rapid change in the composition of the solution around a ventricular myocyte results in a slower change in the composition of the fluid within the t-tubules because of the time required for diffusion into the t-tubular network. In guinea pig myocytes, a rapid change of [Ca 2+] o results in the diffusion of Ca 2+ into the t-tubules at 3 to 16 μm/s, 16 so that the solution change within the t-tubules is delayed by up to 2.3 seconds, and washout of Ca 2+ from the t-tubules occurs with a time constant of up to 1.7 seconds for the deeper regions of the t-tubular system, 16 although these time courses may vary between species, 17 possibly reflecting species differences in t-tubule morphology. 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.