Heart sarcoplasmic reticulum

The general picture of muscle contraction in the heart resembles that of skeletal muscle. Cardiac muscle, like skeletal muscle, is striated and uses the actin-myosin-tropomyosin-troponin system described above. Unlike skeletal muscle, cardiac muscle exhibits intrinsic rhyth-micity, and individual myocytes communicate with each other because of its syncytial nature. The T tubular system is more developed in cardiac muscle, whereas the sarcoplasmic reticulum is less extensive and consequently the intracellular supply of Ca for contraction is less. Cardiac muscle thus relies on extracellular Ca for contraction if isolated cardiac muscle is deprived of Ca, it ceases to beat within approximately 1 minute, whereas skeletal muscle can continue to contract without an extraceUular source of Ca +. Cyclic AMP plays a more prominent role in cardiac than in skeletal muscle. It modulates intracellular levels of Ca through the activation of protein kinases these enzymes phosphorylate various transport proteins in the sarcolemma and sarcoplasmic reticulum and also in the troponin-tropomyosin regulatory complex, affecting intracellular levels of Ca or responses to it. There is a rough correlation between the phosphorylation of Tpl and the increased contraction of cardiac muscle induced by catecholamines. This may account for the inotropic effects (increased contractility) of P-adrenergic compounds on the heart. Some differences among skeletal, cardiac, and smooth muscle are summarized in... 

Enzyme Assay. Na , K -ATPase, and sarcoplasmic reticulum Ca - ATPase were prepared from rat hearts (22) and dog hearts (23), respectively. Bovine heart cyclic AMP phosphodiesterase was purchased from Sigma. The enzyme reaction was carried out after 5-min pretreatment with the drug, and the amount of inorganic phosphate liberated during the reaction period was determined. 

Cheng H, Lederer WJ, Cannell MB 1993 Calcium sparks elementary events underlying excitation—contraction coupling in heart muscle. Science 262 740—744 Collier ML, Thomas AP, Berlin JR 1999 Relationship between L-type Ca2+ current and unitary sarcoplasmic reticulum Ca2+ release events in rat ventricular myocytes. J Physiol (Lond)... 

Lukyanenko V, Gyorke I, Wiesner TF, Gyorke S 2001 Potentiation of Ca2+ release by cADP ribose in the heart is mediated by enhanced SR Ca2+ uptake into the sarcoplasmic reticulum. Circ Res 89 614-622... 

A sarcoplasmic reticulum protein, known as phospho-lambam, phosphorylation of which increases the activity of the Ca ion uptake process in the reticulum and hence the concentration of Ca ions in the cytoplasm decreases more rapidly. This results in a decrease in the relaxation time of the muscle and hence an increase in heart rate. 

In the resting state, the Ca "" level in the sarcoplasm is very low (less than 10 M). By contrast, the sarcoplasmic reticulum (SR), which corresponds to the ER, contains Ca "" ions at a concentration of about 10 M. The SR is a branched organelle that surrounds the myofibrils like a net stocking inside the muscle fibers (illustrated at the top using the example of a heart muscle cell). The high Ca "" level in the SR is maintained by Ca ""-transporting ATPases (see p. 220). In addition, the SR also contains calsequestrin, a protein (55 kDa) that is able to bind numerous Ca "" -ions via acidic amino acid residues. 

The vigor of contraction of heart muscle is determined by several processes that lead to the movement of actin and myosin filaments in the cardiac sarcomere (Figure 13-1). Ultimately, contraction results from the interaction of activator calcium (during systole) with the actin-troponin-tropomyosin system, thereby releasing the actin-myosin interaction. This calcium is released from the sarcoplasmic reticulum (SR). The amount released depends on the amount stored in the SR and on the amount of trigger calcium that enters the cell during the plateau of the action potential. 

The bipyridines increase myocardial contractility by increasing inward calcium flux in the heart during the action potential they may also alter the intracellular movements of calcium by influencing the sarcoplasmic reticulum. They also have an important vasodilating effect. Inhibition of phosphodiesterase results in an increase in cAMP and the increase in contractility and vasodilation. 

Digoxin Na +, K+ ATPase inhibition results in reduced Ca2+ expulsion and increased Ca2+ stored in sarcoplasmic reticulum Increases cardiac contractility cardiac parasympathomimetic effect (slowed sinus heart rate, slowed atrioventricular conduction) Chronic symptomatic heart failure rapid ventricular rate in atrial fibrillation Oral, parenteral duration 36-40 h Toxicity Nausea, vomiting, diarrhea cardiac arrhythmias... 

Sodium and potassium are not the only ions which can participate in pumps and channels. Calcium is also pumped, channeled, exhanged,and stored. See Figure 23. Calcium concentration within the cell cytoplasm is very low. This allows the calcium to play a pivotal role in cellular activity. The cytoplasmic protein calmodulin binds and stores calcium ion. Various intracellular structures and organelles such as the mitochondria and sarcoplasmic reticulum also store calcium. Calcium is vital to such functions as the release of neurotransmitters from nerve cells. There are at least seven known modes of biochemical action for this ion, one of the most important of which involves stimulation of cardiac muscle protein (actin-myosin). Certain types of angina (heart pain) are believed to be caused by abnormal stimulation of cardiac arteries and muscle (coronary spasm) A relatively new class of drugs, known as the calcium channel blockers, has brought relief from pain and arrhythmias (irregular heart beats). 

Zucchi R, Yu G, Ghelardoni S, RoncaF, Ronca-Testoni S (2001) Aj adenosine receptor stimulation modulates sarcoplasmic reticulum Ca2+ release in rat heart. Cardiovasc Res 50(l) 56-64. 

Annexins 1, 2, 4, 5, 6 and 7 have all been identified in the heart, though annexins 5 and 6 are by far the most abundant. Due to the fluctuating levels of submembranous calcium all annexins would be expected to exhibit dynamic on-off interactions with sarcolemal and sarcoplasmic reticulum membranes in cardiomyocytes upon exitation and calcium influx (reviewed in Camors et al., 2005). 

Kiewitz R, Acklin C, Schafer BW, Maco B, Uhrik B, Wuytack F, Erne P, Heizmann CW. 2003. Ca2+ -dependent interaction of S100A1 with die sarcoplasmic reticulum Ca2+ -ATPase2a and phospholamban in the human heart. Biochem Biophys Res Commun 306(2) 550-557. 

Netticadan, T., Temsah, R. M., Kent, A., Elimban, V., and Dhalla, N. S. (2001). Depressed Levels of Ca2+-Cycling Proteins May Underlie Sarcoplasmic Reticulum Dysfunction in the Diabetic Heart. Diabetes 50(9) 2133-8. 

Teshima, Y., Takahashi, N., Saikawa, T., Hara, M., Yasunaga, S., Hidaka, S., and Sakata, T. (2000). Diminished Expression of Sarcoplasmic Reticulum Ca2+-ATPase and Ryanodine Sensitive Ca2+ Channel mRNA in Streptozotocin-Induced Diabetic Rat Heart. J Mol Cell Cardiol 32(4) 655-64. 

Ver Heyen, M., Heymans, S., Antoons, G., Reed, T., Periasamy, M., Awede, B., Lebacq, J., Vangheluwe, P., Dewerchin, M., Collen, D., Sipido, K., Carmeliet, P., and Wuytack, F., 2001, Replacement of the muscle-specific sarcoplasmic reticulum Ca(2+)-ATPase isoform SERCA2a by the nonmuscle SERCA2b homologue causes mild concentric hypertrophy and impairs contraction-relaxation of the heart. Circ Res, 89 838 16. 

During heart failure (HF), functional expression of different proteins involved in E-C coupling is altered, and these changes contribute to altered Ca transients, contractility and arrhythmias in HF. Furthermore, genetic mutations in the key Ca-cycling proteins have been recently identified, which contribute to heart failure and fatal arrhythmias. This chapter will concentrate in recent studies on genetic modifiers of cardiac function at the level of the sarcoplasmic reticulum. 

Hobai, I.A., O Rourke, B. 2001, Decreased sarcoplasmic reticulum calcium content is responsible for defective excitation-contraction coupling in canine heart failure. Circulation, 103(11), pp 1577-84. 

Lindner, M., Erdmann, E., and Beuckelmann, D.J., 1998, Calcium content of the sarcoplasmic reticulum in isolated ventricular myocytes from patients with terminal heart failure. J Mol Cell Cardiol, 30(4), pp 743-9. 

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