T-tubules (transverse tubules) are extensions of the cell membrane that penetrate into the center of skeletal and cardiac muscle cells. With membranes that contain large concentrations of ion channels, transporters, and pumps, T-tubules permit rapid transmission of the action potential into the cell, and also play an important role in regulating cellular calcium concentration.
Through these mechanisms, T-tubules allow heart muscle cells to contract more forcefully by synchronising calcium release from the sarcoplasmic reticulum throughout the cell. T-tubule structure and function are affected beat-by-beat by cardiomyocyte contraction, as well as by diseases, potentially contributing to heart failure and arrhythmias. Although these structures were first seen in 1897, research into T-tubule biology is ongoing.
Structure
T-tubules are tubules formed from the same phospholipid bilayer as the surface membrane or sarcolemma of skeletal or cardiac muscle cells. They connect directly with the sarcolemma at one end before travelling deep within the cell, forming a network of tubules with sections running both perpendicular (transverse) to and parallel (axially) to the sarcolemma. Due to this complex orientation, some refer to T-tubules as the transverse-axial tubular system. The inside or lumen of the T-tubule is open at the cell surface, meaning that the T-tubule is filled with fluid containing the same constituents as the solution that surrounds the cell (the extracellular fluid). Rather than being just a passive connecting tube, the membrane that forms T-tubules is highly active, being studded with proteins including L-type calcium channels, sodium-calcium exchangers, calcium ATPases and Beta adrenoceptors.
T-tubules are found in both atrial and ventricular cardiac muscle cells (cardiomyocytes), in which they develop in the first few weeks of life. They are found in ventricular muscle cells in most species, and in atrial muscle cells from large mammals. In cardiac muscle cells, across different species, T-tubules are between 20 and 450 nanometers in diameter and are usually located in regions called Z-discs where the actin myofilaments anchor within the cell. T-tubules within the heart are closely associated with the intracellular calcium store known as the sarcoplasmic reticulum in specific regions referred to as terminal cisternae. The association of the T-tubule with a terminal cistern is known as a diad.
In skeletal muscle cells, T-tubules are three to four times narrower than those in cardiac muscle cells, and are between 20 and 40 nm in diameter. They are typically located at either side of the myosin strip, at the junction of overlap (A-I junction) between the A and I bands. T-tubules in skeletal muscle are associated with two terminal cisternae, known as a triad.
Regulators
The shape of the T-tubule system is produced and maintained by a variety of proteins. The protein amphiphysin-2 is encoded by the gene BIN1 and is responsible for forming the structure of the T-tubule and ensuring that the appropriate proteins (in particular L-type calcium channels) are located within the T-tubule membrane. Junctophilin-2 is encoded by the gene JPH2 and helps to form a junction between the T-tubule membrane and the sarcoplasmic reticulum, vital for excitation-contraction coupling. Titin capping protein known as telethonin is encoded by the TCAP gene and helps with T-tubule development and is potentially responsible for the increasing number of T-tubules seen as muscles grow.
Function
Excitation-contraction coupling
T-tubules are an important link in the chain from electrical excitation of a cell to its subsequent contraction (excitation-contraction coupling). When contraction of a muscle is needed, stimulation from a nerve or an adjacent muscle cell causes a characteristic flow of charged particles across the cell membrane known as an action potential. At rest, there are fewer positively charged particles on the inner side of the membrane compared to the outer side, and the membrane is described as being polarised. During an action potential, positively charged particles (predominantly sodium and calcium ions) flow across the membrane from the outside to the inside. This reverses the normal imbalance of charged particles and is referred to as depolarization. One region of membrane depolarizes adjacent regions, and the resulting wave of depolarization then spreads along the cell membrane. The polarization of the membrane is restored as potassium ions flow back across the membrane from the inside to the outside of the cell.