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Cardiac muscle edit
There are two types of cardiac muscle cells: autorhythmic and contractile. Autorhythmic cells do not contract, but instead set the pace of contraction for other cardiac muscle cells, which can be modulated by the autonomic nervous system. In contrast, contractile muscle cells, called cardiomyocytes, constitute the majority of the heart muscle and are able to contract.
Excitation-contraction coupling edit
In both skeletal and cardiac muscle excitation-contraction (E-C) coupling, depolarization conduction and Ca2+ release processes occur. However, though the proteins involved are similar, they are distinct in structure and regulation. The dihydropyridine receptors (DHPRs) are encoded by different genes, and the ryanodine receptors (RyRs) are distinct isoforms. Besides, DHPR contacts with RyR1 (main RyR isoform in skeletal muscle) to regulate Ca2+ release in skeletal muscle, while the L-type calcium channel (DHPR on cardiac myocytes) and RyR2 (main RyR isoform in cardiac muscle) are not physically coupled in cardiac muscle, but face with each other by a junctional coupling.[1]
Unlike skeletal muscle, E-C coupling in cardiac muscle is thought to depend primarily on a mechanism called calcium-induced calcium release[2], which is based on the junctional structure between T-tubule and sarcoplasmic reticulum. Junctophilin-2 (JPH2) is essential to maintain this structure, as well as the integrity of T-tubule.[3][4][5] Another protein, receptor accessory protein 5 (REEP5), functions to keep the normal morphology of junctional SR.[6] Defects of junctional coupling can result from deficiencies of either of the two proteins. During the process of calcium-induced calcium release, RyR2s are activated by a calcium trigger, which is brought about by the flow of Ca2+ through the L-type calcium channels. After this, cardiac muscle tends to exhibit diad (or dyad) structures, rather than triads.
Excitation-contraction coupling in cardiac muscle cells occurs when an action potential is initiated by pacemaker cells in the sinoatrial node or Atrioventricular node and conducted to all cells in the heart via gap junctions. The action potential travels along the surface membrane into T-tubules, found in only some cardiac cell types, and the depolarization causes extracellular Ca2+
to enter the cell via L-type calcium channels and possibly sodium-calcium exchanger (NCX) during the early part of the plateau phase. Although this Ca2+ influx accounts for only about 10% of the Ca2+ needed for activation, it is relatively larger than that of skeletal muscle. The increase of intracellular Ca2+
is detected by RyR2 in the membrane of the sarcoplasmic reticulum, which releases Ca2+
in a positive feedback physiological response. This positive feedback is known as calcium-induced calcium release[2] and gives rise to calcium sparks (Ca2+
sparks[7]). The spatial and temporal summation of ~30,000 Ca2+
sparks gives a cell-wide increase in cytoplasmic calcium concentration.[8] The increase in cytosolic calcium following the flow of calcium through the cell membrane and sarcoplasmic reticulum is moderated by calcium buffers such as calsequestrin and parvalbumin, proteins that bind to a large proportion of intracellular calcium. As a result, a large increase in total calcium leads to a relatively small rise in free Ca2+
.[9]
The cytoplasmic calcium binds to Troponin C, moving the tropomyosin complex off the actin binding site allowing the myosin head to bind to the actin filament. From this point on, the contractile mechanism is essentially the same as that for skeletal muscle (above). Briefly, using ATP hydrolysis, the myosin head pulls the actin filament toward the centre of the sarcomere.
Following systole, intracellular calcium is taken up by the sarco/endoplasmic reticulum ATPase (SERCA) and pumped back into the sarcoplasmic reticulum in preparation for the next cycle. Calcium is also ejected from the cell mainly by the sodium-calcium exchanger (NCX) and to a lesser extent through a plasma membrane calcium ATPase. Some calcium is also taken up by the mitochondria.[10] The protein phospholamban serves as a brake for SERCA. At low heart rates, phospholamban is active and slows down the activity of the ATPase so that Ca2+
does not have to leave the cell entirely. At high heart rates, phospholamban is phosphorylated and deactivated thus taking most Ca2+
from the cytoplasm back into the sarcoplasmic reticulum. Calcium buffers moderate this fall in Ca2+
concentration, permitting a relatively small decrease in free Ca2+
concentration in response to a large change in total calcium. The falling Ca2+
concentration allows the troponin complex to dissociate from the actin filament thereby ending contraction. The heart relaxes, allowing the ventricles to fill with blood and begin the cardiac cycle again.
- ^ Martonosi, Anthony N.; Pikula, Slawomir (2003). "The network of calcium regulation in muscle". Acta Biochimica Polonica. 50 (1): 1–30. ISSN 0001-527X. PMID 12673344.
- ^ a b Fabiato, A. (1983). "Calcium-induced calcium release from the cardiac sarcoplasmic reticulum". American Journal of Physiology. 245 (1): C1–14. doi:10.1152/ajpcell.1983.245.1.C1. PMID 6346892.
- ^ Guo, Ang; Zhang, Xiaoying; Iyer, Venkat Ramesh; Chen, Biyi; Zhang, Caimei; Kutschke, William J.; Weiss, Robert M.; Franzini-Armstrong, Clara; Song, Long-Sheng (2014-08-19). "Overexpression of junctophilin-2 does not enhance baseline function but attenuates heart failure development after cardiac stress". Proceedings of the National Academy of Sciences of the United States of America. 111 (33): 12240–12245. doi:10.1073/pnas.1412729111. ISSN 1091-6490. PMC 4143026. PMID 25092313.
- ^ Wei, Sheng; Guo, Ang; Chen, Biyi; Kutschke, William; Xie, Yu-Ping; Zimmerman, Kathy; Weiss, Robert M.; Anderson, Mark E.; Cheng, Heping; Song, Long-Sheng (2010-08-20). "T-tubule remodeling during transition from hypertrophy to heart failure". Circulation Research. 107 (4): 520–531. doi:10.1161/CIRCRESAHA.109.212324. ISSN 1524-4571. PMC 2927862. PMID 20576937.
- ^ Takeshima, H.; Komazaki, S.; Nishi, M.; Iino, M.; Kangawa, K. (2000-07). "Junctophilins: a novel family of junctional membrane complex proteins". Molecular Cell. 6 (1): 11–22. doi:10.1016/s1097-2765(00)00003-4. ISSN 1097-2765. PMID 10949023.
{{cite journal}}: Check date values in:|date=(help) - ^ Yao, Lei; Xie, Duanyang; Geng, Li; Shi, Dan; Huang, Jian; Wu, Yufei; Lv, Fei; Liang, Dandan; Li, Li; Liu, Yi; Li, Jun (02 03, 2018). "REEP5 (Receptor Accessory Protein 5) Acts as a Sarcoplasmic Reticulum Membrane Sculptor to Modulate Cardiac Function". Journal of the American Heart Association. 7 (3). doi:10.1161/JAHA.117.007205. ISSN 2047-9980. PMC 5850239. PMID 29431104.
{{cite journal}}: Check date values in:|date=(help) - ^ Cheng H, Lederer WJ, Cannell MB (October 1993). "Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle". Science. 262 (5134): 740–4. Bibcode:1993Sci...262..740C. doi:10.1126/science.8235594. PMID 8235594.
- ^ Cannell MB, Cheng H, Lederer WJ (November 1994). "Spatial non-uniformities in Ca2+
i during excitation-contraction coupling in cardiac myocytes". Biophys. J. 67 (5): 1942–56. Bibcode:1994BpJ....67.1942C. doi:10.1016/S0006-3495(94)80677-0. PMC 1225569. PMID 7858131. - ^ M., Bers, D. (2001). Excitation-contraction coupling and cardiac contractile force (2nd ed.). Dordrecht: Kluwer Academic Publishers. ISBN 9780792371571. OCLC 47659382.
{{cite book}}: CS1 maint: multiple names: authors list (link) - ^ Crespo LM, Grantham CJ, Cannell MB (June 1990). "Kinetics, stoichiometry and role of the Na-Ca exchange mechanism in isolated cardiac myocytes". Nature. 345 (6276): 618–21. Bibcode:1990Natur.345..618C. doi:10.1038/345618a0. PMID 2348872.