T-Tubule Function in Mammalian Cardiac Myocytes

Abstract

Abstract-The transverse tubules (t-tubules) of mammalian cardiac ventricular myocytes are invaginations of the surface membrane. Recent studies have suggested that the structure and function of the t-tubules are more complex than previously believed; in particular, many of the proteins involved in cellular Ca 2ϩ cycling appear to be concentrated at the t-tubule. Thus, the t-tubules are an important determinant of cardiac cell function, especially as the main site of excitation-contraction coupling, ensuring spatially and temporally synchronous Ca 2ϩ release throughout the cell. Changes in t-tubule structure and protein expression occur during development and in heart failure, so that changes in the t-tubules may contribute to the functional changes observed in these conditions. The purpose of this review is to provide an overview of recent studies of t-tubule structure and function in cardiac myocytes. Key Words: cardiac muscle Ⅲ t-tubules Ⅲ excitation-contraction coupling Ⅲ heart failure T he transverse tubules (t-tubules) of mammalian cardiac ventricular myocytes are invaginations of the surface membrane that occur at the Z line and have both transverse and longitudinal elements. Many of the proteins involved in excitation-contraction coupling appear to be concentrated at the t-tubules. Therefore, it has been suggested that the t-tubules play a central role in cell activation. In the present review, we will consider the immunohistochemical and functional evidence for protein localization at the t-tubules, potential problems in the interpretation of such data, and the functional consequences of such localization. We will also consider the possible role of the t-tubules in the functional changes that occur during cardiac development, hypertrophy, and failure. Occurrence and Morphology of the T-TubulesT-tubules are present in the cardiac tissue of all species of mammals so far investigated (eg, mice, 1 rats, 2 guinea pigs, 3 rabbits, 4 dogs, 5 pigs, 1 and humans 6 ) but appear to be absent in avian, 7 reptile 8 and amphibian 8 cardiac tissue. Within mammalian cardiac tissue, t-tubules occur predominantly in ventricular myocytes, being either absent or far less developed in atrial, pacemaking, and conducting tissue, 9 although a recent report has suggested that Ϸ50% of atrial myocytes possess a sparse irregular tubular system. 10 The following discussion will concentrate on mammalian ventricular myocytes.The t-tubules are invaginations of the sarcolemma and glycocalyx, which appears to remain associated with the sarcolemma within the t-tubules. 11 Early studies of cardiac muscle showed that they occur at the Z line, at the end of each sarcomere 12 ; therefore, they occur at intervals of Ϸ2 m along the longitudinal axis of the ventricular myocyte. Subsequent studies have shown that the t-tubular system also has longitudinal extensions. 13 Although the t-tubules leave the surface membrane at the Z line, forming an approximately rectangular array, only Ϸ60% of the tubular volume occurs near the Z line; the other 40% ...

Action potential propagation in transverse-axial tubular system is impaired in heart failure

“…We achieved a physical disconnection of TTs from SS (acute detubulation) with an osmotic shock technique (24). When the two membrane systems were electrically uncoupled, the SS AP was shorter (6), which is consistent with the excess of L-type Ca 2+ current in TATS (Fig. S6).…”

“…The coupling between sarcolemmal Ca 2+ entry during an action potential (AP) and Ca 2+ release from sarcoplasmic reticulum (SR) promotes synchronous myofibril activation throughout the myocyte (5). Recent studies highlight that AP-relevant ion channels and transporters are expressed in TATS membrane with different densities and isoforms from those in SS (6,7). These findings, in combination with diffusional limitations in TATS's lumen (3,8), raise the possibility that AP may differ among membrane domains.…”

Myoscape controls cardiac calcium cycling and contractility via regulation of L-type calcium channel surface expression

“…Moreover, it also affects intracellular signalling pathways and gene regulation456. In specific membrane invaginations termed t-tubules, every LTCC faces several ryanodine receptors on the sarcoplasmic reticulum to form a couplon7. Changes in t-tubule density, length, width and in the composition of couplon-associated proteins occur in various disease states, such as cardiac hypertrophy and heart failure8.…”

Sodium Channel Remodeling in Subcellular Microdomains of Murine Failing Cardiomyocytes

“…In line with other studies demonstrating T‐tubule remodeling in HF, we observed less deep Z grooves in TAC cardiomyocytes in addition to less clearly identifiable T‐tubule openings. Apart from the cardiac sodium channel Na V 1.5, neuronal sodium channel isoforms (ie, Na V 1.1, Na V 1.3, and Na V 1.6) are also thought to populate the T tubules 29, 30, 31, 32. Studies on expression and function of neuronal sodium channel isoforms during HF have shown varied results, most likely because of variations in species (rat, rabbit, dog) and HF model (pressure and/or volume overload and embolizations) used, with the most consistent observation comprising an upregulation of Na V 1.1 5, 23, 33.…”