Muscle-cell surface skeletal

AT-tubule is a transverse invagination of the sarcolem-ma, which occurs at characteristic sites in animal species and organs, i.e. at the Z-membrane in cardiac ventricle muscle and non-mammalian vertebrate skeletal muscle and at the A-I junction in mammalian skeletal muscle. It is absent in all avian cardiac cells, all cardiac conduction cells, many mammalian atrial cells and most smooth muscle cells. It serves as an inward conduit for the action potential. The surface area in the skeletal muscle can reach 6-8 times that of a cylinder with the same radius. In the T-tubule, Na-channel, Ca-channel and other important channels and transporters can be detected. 

The entry rate of glucose into red blood cells is far greater than would be calculated for simple diffusion. Rather, it is an example of facilitated diffiision (Chapter 41). The specific protein involved in this process is called the glucose transporter or glucose permease. Some of its properties are summarized in Table 52-3-The process of entry of glucose into red blood cells is of major importance because it is the major fuel supply for these cells. About seven different but related glucose transporters have been isolated from various tissues unlike the red cell transporter, some of these are insidin-dependent (eg, in muscle and adipose tissue). There is considerable interest in the latter types of transporter because defects in their recruitment from intracellular sites to the surface of skeletal muscle cells may help explain the insulin resistance displayed by patients with type 2 diabetes mellitus. 

Beside this there are some major differences with the neurotransmission in the autonomous nervous system The contractile activity of the skeletal muscle is almost completely dependent on the innervation. There is no basal tone and a loss of the innervation is identical to a total loss in function of the particular skeletal muscle. In contrast to the target organs of the parasympathetic nervous system the skeletal muscle cells only have acetylcholine receptors at the site of the so-called end-plate, the connection between neuron and muscle cell with the rest of the cell surface being insensitive to the transmitter. The release of acetylcholine results in a postjunctional depolarization which is either above the threshold to induce an action potential and a contraction or below the threshold with no contractile response at all. In contrast to the graduated reactions of the parasympathetic target organs, this is an all or nothing transmission. 

If compared to the neuro muscular junction at skeletal muscle the diffusion distance for the transmitter in the synaptic cleft is much longer. Furthermore, the membrane of the target cell is not specialized at the site of the junction but has receptors at the whole surface. In contrast to the all or nothing response of the skeletal muscle cell, the response of the sympathetic target cell to the transmitter is concentration-proportional, or graduated. 

The absorption of sulfonylureas from the upper gastrointestinal tract is fairly rapid and complete. The agents are transported in the blood as protein-bound complexes. As they are released from protein-binding sites, the free (unbound) form becomes available for diffusion into tissues and to sites of action. Specific receptors are present on pancreatic islet p-cell surfaces which bind sulfonylureas with high affinity. Binding of sulfonylureas to these receptors appears to be coupled to an ATP-sensitive K+ channel to stimulate insulin secretion. These agents may also potentiate insulin-stimulated glucose transport in adipose tissue and skeletal muscle. 

In muscle cells, the contraction is induced by Ca2+ release from the sarcoplasmic reticulum, as a result of membrane depolarization and activation of RyRl receptors located at the surface of the SR. The subsequent transport of cytoplasmic Ca2+ back into the lumen of the sarcoplasmic reticulum restores low resting calcium levels and allows muscle relaxation. In fast-twitch skeletal muscle fibers, Ca2+ uptake is mediated by the sarco(endo)plasmic reticulum Ca2+ ATPase SERCA1 which represents more than 99% of SERCA isoforms in these muscle fibers. 

It appears that insulin and certain growth factors may exert their effects by acting through this type of tyrosine kinase receptor-enzyme system.21,44 Insulin, for example, binds to the extracellular component of a protein located on skeletal muscle cells, thereby initiating activation of this protein s enzymatic activity on the inner surface of the cell membrane. This change in enzyme function causes further changes in cell activity, which ultimately result in increased glucose uptake in the muscle cell. The function of insulin receptors and their role in the cause and treatment of diabetes mellitus are discussed in more detail in Chapter 32. 

The release of fatty acids from adipose tissue is regulated by the rate of hydrolysis of triacylglycerol and the rate of esterification of acyl-CoA with glycerol 3-phosphate. The rate of hydrolysis is stimulated by hormones that bind to cell-surface receptors and stimulate adenylate cyclase (which catalyzes the production of cAMP from ATP). Hormone-sensitive lipase (Sec. 13.4) can exist in two forms, one of which exhibits very low activity and a second which is phosphorylated and has high activity. Before hormonal stimulation of adenylate cyclase, the low-activity lipase predominates in the fat cell. Stimulation of protein kinase by an increase in cAMP concentration leads to phosphorylation of the low-activity lipase. An increase in the rate of hydrolysis of triacylglycerol and the release of fatty acids from the fat cell follows. This leads to a greater utilization of fatty acids by tissues such as heart, skeletal muscle, and liver. 

Insulin-sensitive tissues, such as skeletal muscle and adipose tissue, contain GLUT4, whose mobilisation to the cell surface is stimulated by insulin action. 

C. M. Wilson and S. W. Cushman. Insulin stimulation of glucose transport activity in rat skeletal muscle. Increase in cell surface GLUT4 as assessed by photo labelling. Biochem. J., 299, 755-759, 1994. 

Cubic membranes have also been foimd in Aves. The study by Ishikawa [18] on the development of the transverse tubule membrane (T-tubule) system in cultured skeletal muscle cells derived from chick embryo represents one of the more arresting examples of cubic membranes that are produced as invaginations of the PM. Indeed, Ishikawa s model for the T-tubule is in many respects similar to that of cubic membranes. Although there were no comments in the original report [18] regarding the symmetry of the "tubular network", the model is in many respects similar to the D-surface. 

Smooth muscle is much more dependent on entry of extracellular calcium. Smooth muscle cells are much smaller, having lengths about equal to the diameter of small skeletal muscle fibers, and so have much bigger surface-to-volume ratios than skeletal muscle cells. Therefore, Ca " " entry from the extracellular space can increase cytoplasmic [Ca +] much more readily in smooth muscle than in skeletal muscle. Most smooth muscle accordingly need not depend on Ca + release from SR, may not have much SR, and does not need action potentials to trigger SR Ca + release. 

The cristae greatly expand the surface area of the inner mitochondrial membrane, enhancing its ability to generate ATP (see Figure 8-6). In typical liver mitochondria, for example, the area of the inner membrane including cristae is about five times that of the outer membrane. In fact, the total area of all inner mitochondrial membranes in liver cells is about 17 times that of the plasma membrane. The mitochondria in heart and skeletal muscles contain three times as many cristae as are found in typical liver mitochondria— presumably reflecting the greater demand for ATP by muscle cells. 

The ensuing discussion will deal with that major category of receptors that are essentially components of cellular membranes. For example, the acetylcholine receptor involving skeletal muscles exerts its effect at the end of the motor nerve and its junction with the muscle (neuromuscular junction, see Chapter 7) by a depolarizing action. The fact that receptors are embedded in muscle cell membranes can be surmised by the fact that the contractile effect can be initiated by simply applying acetylcholine to the surface of the muscle preparation intracellular injection of the agonist produces no effect. A more interesting... 

GLUT 4 Adipose tissue Skeletal muscle Heart muscle Insulin-sensitive transporter. In the presence of insulin the number of GLUT 4 transporters increases on the cell surface. A high-affinity system... 

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