Heart and Skeletal Muscle

In an early investigation an attempt was made to study the localization and fate of labeled lysolecithin in the heart, with the help of radioautography. Rat hearts were labeled by perfusion with either 

26 (top) and 27 (bottom). Sections of rat heart pulse labeled for 30 seconds with oleic acid- H and chased for 15 seconds (Fig. 26) or 2 minutes (Fig. 27). The grains are seen over subsarcolemmal cistemae of the sarcoplasmic reticulum (Fig. 26) over mitochondria and other elements of the sarcoplasmic reticulum. The lipid droplets in the preparation chased for 2 minutes are labeled more heavily. Fig. 26, X 19,000 Fig. 27, X 26,000. (From O. Stein and Stein, 1968, reproduced by permission of the Editor of J. Cell Biol.) 

Another finding revealed by radioautography was the accumulation of label over lipid droplets with time of perfusion (Fig. 4), which indicated that the triglyceride deposited in droplet form has a turnover rate slower than that located in the intracellular organelles. 

The uptake of palmitic acid- K] by the pectoralis muscle of pigeons from the circulation was studied 3-15 minutes after its intravenous injection (Wirsen, 1965). Radioautography was carried out with non-fixed frozen sections, using X-ray film. The radioautographic reaction was much more pronounced over red than over white fibers, but as no analysis of the labeled lipid within die muscle is given it is not possible to determine whether the reaction is due to free fatty acid, triglyceride, or phospholipid. 

The heart was found to be enlarged in all autopsied cases. Its weight in the 47 year-old patient of Scriba (1950) was 550 gm, in the 47 year-old patient (case 3) of Colley et al. (1958) 630 gm and in the 38 year-old patient reported by Falck and Weicksel (1957) 620 gm. Although both ventricles are hypertrophied, the musculature of the right heart may be thicker than that of the left (Scriba 1950). 

Microscopic examination shows widening and hypertrophy of muscle fibers. Numerous muscle cells are vacuolated. Vacuoles are particularly numerous in the center of muscle fibers and displace the muscle fibrils peripherally (Scriba 1950). In a patient described by Leder and Bosworth (1965) who, in addition to ACD, suffered from mitral stenosis, there was edematous, fibrous thickening of the endocardium of the left auricular appendix, which extended into the interstitium. The nuclei of involved cells are usually large, rarely pyknotic they frequently appear irregularly outlined, lobulated and hyperchromatic (Ruiter et al. 1947, Scriba 1950, Hornbostel 1952, Leder and Bosworth 1965). 

The material which is stored in the heart muscle is birefringent (Scriba 1950) and stains faintly yellowish-red with hematoxylin-scarlet red. 

Involvement of the skeletal musculature is qualitatively similar to that of the heart muscle, although storage is less marked and a predilection of vacuoles for the center of muscle fibers is not apparent. 

Histochemical properties of skin vessels are similar to those of the vasculature of other tissues. The diagnosis of ACD is therefore established most easily by means of a skin biopsy. Ruiter (1954), Pittelkow et al. (1957), de Groot (1961,1964), VON Gemmingen (1965) have described specific staining methods for the stored lipid. Although its histochemical behaviour resembles that of phospholipids, Lapiere (1957) could not find increased phosphatides upon chemical analyses. In most other cases chemical analyses were not performed. 

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Figure 12-14. The creatine phosphate shuttle of heart and skeletal muscle. The shuttle allows rapid transport of high-energy phosphate from the mitochondrial matrix into the cytosol. CKg, creatine kinase concerned with large requirements for ATP, eg, muscular contraction CIC, creatine kinase for maintaining equilibrium between creatine and creatine phosphate and ATP/ADP CKg, creatine kinase coupling glycolysis to creatine phosphate synthesis CK, , mitochondrial creatine kinase mediating creatine phosphate production from ATP formed in oxidative phosphorylation P, pore protein in outer mitochondrial membrane.

GLUT 4 Heart and skeletal muscle, adipose tissue Insulin-stimulated uptake of glucose... 

Free fatty acids are removed from the blood extremely rapidly and oxidized (fulfilling 25-50% of energy requirements in starvation) or esterified to form triacylglycerol in the tissues. In starvation, esterified lipids from the circulation or in the tissues are oxidized as well, particularly in heart and skeletal muscle cells, where considerable stores of lipid are to be found. 

Doege, H., et al. Characterization of human glucose transporter (GLUT) 11 (encoded by SLC2A11), a novel sugar-transport facilitator specifically expressed in heart and skeletal muscle. Biochem. J. 2001, 359, 443-449. 

Van Helden PD, Wild IJ (1982) Effects of adriamycin on heart and skeletal muscle chromatin. Biochem Pharmacol 31(6) 973-977... 

The increased oxidation of fatty acids decreases the rate of glucose utilisation and oxidation by muscle, via the glucose/fatty acid cycle, which accounts for some of the insulin resistance in trauma. An additional factor may be the effect of cytokines on the insulin-signalling pathway in muscle. An increased rate of fatty acid oxidation in the liver increases the rate of ketone body production the ketones will be oxidised by the heart and skeletal muscle, which will further reduce glucose utilisation. This helps to conserve glucose for the immune and other cells. 

Upcn hydrogenation, fish oils, especially the longer chain fatty acids (C22 s), form many new positional and geometric isomers. In some cases, partially hydrogenated fish oils may contain as many as 50% of the docosenoic acids in the trans form as opposed to the naturally occurring cis form. It is these trans isomers which may be responsible for the lipidosis of heart and skeletal muscle found in monkeys. Epidemiological studies of populations with high intakes of docosenoic acids. 

Musculoskeletal/Cardiac effects When serum sodium or calcium concentration is reduced, moderate elevation of serum potassium may cause toxic effects on the heart and skeletal muscle. Weakness and later paralysis of voluntary muscles, with consequent respiratory distress and dysphagia, are generally late signs, sometimes significantly preceding dangerous or fatal cardiac toxicity. 

CN184 Plot. C., ]. F. Hocquette, ]. H. Veerkamp, D. Durand, and D. Bauchart. Effects of dietary coconut oil on fatty acid oxidation capacity of the liver, the heart and skeletal muscles in... 

Vaidya, H. Dietzler, D.N. Leykam, J.R Ladenson, J.H. Purification of five creatine kinase-MM variants from human heart and skeletal muscle. Biochim. Biophys. Acta, 790, 230-237 (1984)... 

Schneider, C. Stull, G.A. Apple, F.S. Kinetic characterization of human heart and skeletal muscle CK isoenzymes. Enzyme, 39, 220-226 (1988)... 

Sodium ion channels in the plasma membranes of neurons and of myocytes of heart and skeletal muscle sense... 

Myoglobin (Mb) consists of one heme group bound to a single polypeptide. It is present in heart and skeletal muscle. Mb functions both as a reservoir for oxygen, and as an oxygen carrier within the muscle cell. 

Making use of the binding of radioactively labeled specific toxins to identify diem, the subunits of the sodium channel proteins were purified from several sources including die electrical tissue of the electric eel Electrophorus electricus,i37 i39 heart and skeletal muscle, and brain.440-44113 In all cases a large 260-kDa glycoprotein, which may be 30% carbohydrate, is present. The saxitoxin-binding protein from rat brain has two additional 33-36 kDa subunits witii a stoichiometry of a(31P2- The Electrophorus a subunit consists of 1820 residues,437 while rat brain contains a proteins of 2009... 

Beckman et al. (28) have studied the electrophoretic separation of the acid phosphatase activity in tissue extracts on starch gel at pH 8. They described four electrophoretic bands A, B, C, and D. Table IV (28) shows the distribution of activity in different organ extracts. The ABD pattern predominated in kidney BD in liver, intestine, heart, and skeletal muscle B in skin and D in pancreas. The C component was present in a large number of placentae but not in other adult organs. All four electrophoretic components were inhibited by d-(- -)-tartrate A contained sialic acid, D had a lower pH optimum and was more heat resistant than A, B, and C. Components C and D showed parallel electrophoretic behavior. In human skin fibroblasts grown in tissue culture, the acid phosphatase was generally high and the most common pattern was BD. Almost every culture showed some activity. The BD... 

Ziada AM, Hudlicka O, Tyler KR, Wright AJ (1984) The effect of long-term vasodilatation on capillary growth and performance in rabbit heart and skeletal muscle. Cardiovas Res 18(12) 724-732... 

Syncoilin is highly expressed in skeletal and cardiac muscle and is localized to the neuromuscular junction, sarcolemma, and Z-lines. Likewise, desmuslin is expressed in heart and skeletal muscle and localized at Z-lines. It was shown that syncoilin and desmin interact directly, but do not coassemble into filaments in fact, evidence suggests that syncoilin does not participate in filament formation at all. It was proposed that syncoilin helps anchor the desmin IF network at the sarcolemma and the neuromuscular junction (Poon et al, 2002). More recent work has analyzed patients with a desmin-related cardiomyopathy in which patients with desmin accumulation also exhibit an upregulation of syncoilin and accumulation of other elements of the DPC. These defects were correlated with a disappearance of both o-dystrobrevin-l and neuronal nitric oxide... 

CM and VLDL secreted by intestinal cells and VLDL synthesized and secreted in the liver have similar metabolic fates. After secretion into the blood, newly formed CM and VLDL take up apoprotein (apo-C) from HDL and are subsequently removed from the blood (plasma half-life of less than 1 h in humans [137]) primarily by the action of lipoprotein lipase (LPL). Lipoprotein lipase is situated mainly in the vascular bed of the heart, skeletal muscle, and adipose tissue and catalyzes the breakdown of core TG to monoglycerides and free fatty acids, which are taken up into adjacent cells or recirculated in blood bound to albumin. The activity of LPL in the heart and skeletal muscle is inversely correlated with its activity in adipose tissue and is regulated by various hormones. Thus, in the fasted state, TG in CM and VLDL is preferentially delivered to the heart and skeletal muscle under the influence of adrenaline and glucagon, whereas in the fed state, insulin enhances LPL activity in adipose tissue, resulting in preferential uptake of TG into adipose tissue for storage as fat. 

Tjfam-deficient mice (Heart and skeletal muscle-specific Tfam knockout) MtDNA depletion, respiratory chain deficiency Dilated cardiomyopathy, atrioventricular heart conduction blocks W4... 

Wasp and hornet venoms are distinguished from bee venoms by their lower content of peptides. They contain kinin peptide, which may cause smooth muscle contraction and lowered blood pressure. Two biogenic amines in wasp and hornet venoms (serotonin and acetylcholine) lower blood pressure and cause pain. Acetylcholine may cause malfunction of heart and skeletal muscles. 

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