The Dystrophin-Glycoprotein Complex & Creatinol-o-phosphate
Thoughout the duration of this discussion it has been made quite apparent that the sarcolemma is important to skeletal muscle function. We have established thus that it plays a central role in the neuromuscular junction which controls excitation/contraction coupling. However, I still haven’t explained the importance of this with regards to recruitment of muscular motor units but we’ll get to the eventually. I guess it’s safe to say I have some ADD when it comes to reading a large body of research.
Regardless, one topic I have stumbled across which I find important for trying to ellucidate the importance of an enhanced sarcolemmal membrane through supplementation is the role this has on actual force production. Without going into great detail, dystrophin is a large sarcolemmal protein molecule greatly responsible for the interaction of the cytoskeleton and the basement membrane in skeletal muscle (1).
In essence, while performing the eccentric motion of an exercise you cause damage to the sarcolemma which causes a loss of dystrophin (2) and ultimately disruption of the dystrophin-glycoprotein complex (DGC)(3,4 ). This disruption impairs the muscles ability to maintain a high level of contractual force (2) and to mediate membrane repair (5).
***Please pardon this interruption with the insertion of another bro-graph!***
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Originally Posted by Physiological Reviews
The dystrophin-associated protein complex (DPC) in skeletal muscle. Dystrophin binds to cytoskeletal actin at its NH2 terminus. At its COOH terminus, dystrophin is associated with a number of integral and peripheral membrane proteins that can be classified as the dystroglycan subcomplex, the sarcoglycan-sarcospan subcomplex, and the cytoplasmic subcomplex. The cytoplasmic subcomplex includes the syntrophins (syn) and -dystrobrevin (DB). The sarcoglycan-sarcopsan subcomplex comprises the sarcoglycans and sarcospan. The extracellular component of the dystroglycan complex, -dystroglycan (DG), binds to laminin-2 in the extracellular matrix and -dystroglycan (DG) in the sarcolemma. In turn, -dystroglycan binds to the dystrophin, thus completing the link between the actin-based cytoskeleton and the extracellular matrix. Additional DPC binding partners are omitted for clarity, but a full list of the proteins can be found in Table 1
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You might have picked up this earlier but dystrophin is in part responsible, or lack thereof, for a disease known as Duchene’s Muscular Dystrophy (6). Essentially, this disease is caused by a genetic mutation and leads to muscular degeneration due to a lack of dystrophin (6-8). With this dabilitating disease eccentric forces cause muscle damage that eventually lead to cell death (6). Many complications come as result and my heart goes out to those who suffer from or have loved one with this affliction.
As you can see, maintenace of the sarcolemmal intregrity with regard to the dystrophin is important. I really wish there was some direct study shows how creatinol-o-phosphate has a positive effect on the DGC. Unfortunately, all of the research was performed decades before the importance of dystrophin and it’s role within skeletal muscle function was known. Eitherway, it’s safe to say that creatinol-o-phosphate enhancement of sarcolemmal integrity does have a postive impact on the DGC and it’s role skeletal muscle force production.
1. Allikian MJ, McNally EM. Processing and Assembly of the Dystrophin Glycoprotein Complex.Traffic. 2007 Jan 30;
2. Lovering RM, De Deyne PG. Contractile function, sarcolemma integrity, and the loss of dystrophin after skeletal muscle eccentric contraction-induced injury.
American Journal of Physiology: Cell Physiology. 2004 Feb;286(2):C230-8.
3. Ehmsen J, Poon E, Davies K.The dystrophin-associated protein complex.Journal of Cell Science. 2002 Jul 15;115(Pt 14):2801-3
4. Michele DE, Campbell KP. Dystrophin-glycoprotein complex: post-translational processing and dystroglycan function. Journal Biological Chemistry. 2003 May 2;278(18):15457-60.
5. Towler MC, Kaufman SJ, Brodsky FM. Membrane traffic in skeletal muscle. Traffic. 2004 Mar;5(3):129-39
6. Deconinck N, Dan B. Pathophysiology of duchenne muscular dystrophy: current hypotheses. Pediatric Neurology. 2007 Jan;36(1):1-7.
7. Allard B. Sarcolemmal ion channels in dystrophin-deficient skeletal muscle fibres.
Journal Muscle Research & Cell Motility. 2006;27(5-7):367-73. Epub 2006 Jul 28.
8. Dudley RW, Danialou G, Govindaraju K, Lands L, Eidelman DE, Petrof BJ. Sarcolemmal damage in dystrophin deficiency is modulated by synergistic interactions between mechanical and oxidative/nitrosative stresses. American Journal of Pathology. 2006 Apr;168(4):1276-87
9.D Blake, A Weir, S Newey, K Davies. Function and Genetics of Dystrophin and Dystrophin-Related Proteins in Muscle. Physiological Reviews. Vol. 82, No. 2, April 2002, pp. 291-329
