Changes in Skeletal Muscle Sarcoplasmic Reticulum Calcium Handling and Regulatory Protein Content in Congestive Heart Failure
Allen, Emily E.
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Fatigue and skeletal muscle weakness are problems associated with congestive heart failure. Research does not support the theory that the affected cardiac function is responsible for the fatigue. During skeletal muscle fatigue, calcium handling is altered. Thus, the fatigue associated with congestive heart failure could be attributed to altered calcium handling. The main proteins involved in calcium release are the ryanodine receptor (RyR) and the dihydropyridine receptor (DHPR). The main proteins involved in calcium uptake are the fast and slow isoforms of sarco(endo)plasmic reticulum calcium ATPase (SERCA 1 and SERCA 2 respectively). Calsequestrin (Csq) and calmodulin (CaM) play regulatory roles in calcium handling. Changes in the levels of these proteins could explain alterations in calcium handling and subsequent muscle function. The purpose of this study was to use a genetic model of heart failure, the SHHF rat, to examine the levels of regulatory calcium handling proteins to determine if changes in the amounts of RyR, DHPR, SERCA1, SERCA2, Csq and CaM are altered in congestive heart failure. A significant decrease was found in the amounts of RyR, DHPR, and SERCA 1 of the SHHF gastrocnemius and diaphragm samples in comparison to the control. There was no significant difference found in the amounts of CaM or SERCA 2 between the two groups. Csq was not found to be statistically different between the two groups of the gastrocnemius samples. However, there was an increase in Csq in the SHHF diaphragm samples in comparison to the control. In conclusion, the calcium handling proteins are affected in the genetic model of heart failure. These changes could explain previous reports of altered calcium handling within the skeletal muscles of congestive heart failure animals.
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