Ca2+-regulatory muscle proteins in the alcohol-fed rat

Alcoholic myopathy is characterized by muscle weakness and difficulties in gait and locomotion. It is one of the most prevalent skeletal muscle disorders in the Western hemisphere, affecting between 40% and 60% of all chronic alcohol misusers. However, the pathogenic mechanisms are unknown, although recent studies have suggested that membrane defects occur as a consequence of chronic alcohol exposure. It was our hypothesis that alcohol ingestion perturbs membrane-located proteins associated with intracellular signalling and contractility, in particular those relating to calcium homeostasis. To test this, we fed male Wistar rats nutritionally complete liquid diets containing ethanol as 35% of total dietary energy. Controls were pair-fed identical amounts of the same diet in which ethanol was replaced by isocaloric glucose. At the end of 6 weeks, rats were killed and skeletal muscles dissected. These were used to determine important ion-regulatory skeletal muscle proteins including sarcalumenin (SAR), sarcoplasmic-endoplasmic reticulum Ca2+-adenosine triphosphatase (ATPase) (SERCA1), the junctional face protein of 90 kd (90-JFP), alpha(1)- and alpha(2)-dihydropyridine receptor (alpha(1)-DHPR and alpha(2)-DHPR), and calsequestrin (CSQ) by immunoblotting. The relative abundance of microsomal proteins was determined by immunoblotting using the enhanced chemiluminescence (ECL) technique. The data showed that alcohol-feeding significantly reduced gastrocnemius and hind limb muscle weights (P < .05 in both instances). Concomitant changes included increases in the relative amounts of SERCA1 (P < .05) and Ca2+-ATPase activity (P < .025). However, there were no statistically significant changes in either SAR, 90-JFP, alpha(1)-DHPR or alpha(2)-DHPR (P > .2 in all instances). Reductions in CSQ were of marginal significance (P = .0950). We conclude that upregulation of SERCA1 protein and Ca2+-ATPase activity may be an adaptive mechanism and/or a contributory process in the pathology of alcohol-induced muscle disease. (C) 2003 Elsevier Inc. All rights reserved.