Acute exercise and digoxin effects on skeletal muscle Na+,K+ATPase regulation, K+ homeostasis and fatigue in humans:

Funded Activity Summary

This grant investigates the regulation of an enzyme in skeletal muscle referred to as the sodium-potassium pump, since its function is to pump potassium into the cell and sodium out of the cell. This enzyme is vital in enabling the muscles to contract and plays a key role in supporting our capacity to exercise. Our studies have suggested that acute exercise depresses the maximal capacity (activity) of this enzyme, thereby rendering the muscle liable to fatigue. We examine whether a well-defined exercise leading to fatigue, does inhibit the sodium-potassium pump and whether recovery occurs within 3 hours after exercise. The sodium-potassium pump is comprised of several variations of very similar enzymes, known as isoforms, each under the control of a separate gene and having slightly different functions and regulation. We explore whether exercise causes the genes regulating these isoforms to be activated and whether this results in an increased isoform formation in the muscle cell. We use a drug commonly used in patients with heart failure, called digoxin, which blocks the action of the sodium-potassium pump. In rat muscles this reduces muscular performance, with earlier and more pronounced fatigue. We examine whether a similar detrimental effect occurs in muscles of exercising humans and measure the resultant effects on muscle sodium and potassium levels. Increased knowledge about the effects of a single exercise bout on muscle is important fundamental knowledge. The study will lead to new knowledge about sodium-potassium pump regulation in exercising humans and thus enhance our understanding of muscle fatigue and gene responses to exercise. Understanding exercise effects will assist in development of strategies to counter physical inactivity, which is a major burden on health in Australia. Improved understanding of the actions of digoxin will also benefit patients with heart failure, through modified drug use and development of more specific treatment.

Funded Activity Details

Start Date: 01-01-2003

End Date: 01-01-2004

Funding Scheme: NHMRC Project Grants

Funding Amount: $177,000.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Basic pharmacology

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

chronic heart failure (CHF) | electrolyte disturbances | exercise | exercise physiology | fatigue | muscle fatigue | potassium homeostasis | skeletal muscle | sodium/potassium [ATPase]

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