Muscle contractions induce cellular potassium (K+) efflux which may contribute to
impaired muscle cell membrane excitability and fatigue. The magnitude of K+ changes
are dependent on the size of contracting muscle mass, duration and intensity of
exercise, and health and fitness status of participants. Activation of the sarcolemmal
and t-tubular bound sodium-potassium adenosine 5’ triphosphatase enzyme
(Na+,K+ATPase, NKA) mediates muscle cell K+ and Na+ active exchange, and is
instrumental in the maintenance of muscle cellular and plasma K+ homeostasis during
exercise. Therefore modulations of NKA function might enhance or impair exercise
induced K+ disturbances, and theoretically can have a profound effect on muscle
excitability and exercise performance. This thesis examined the effects of two
interventions designed to induce acute or short term upregulation and downregulation
of NKA activity on K+ homeostasis and exercise performance in healthy humans. Study
1 investigated the effects of metabolically induced alkalosis on plasma K+ regulation
during submaximal finger flexion (small muscle mass) contractions and fatigue in
healthy humans. Study 2 investigated the effects of a clinically relevant dose of digoxin
administration on K+ regulation, during intermittent supramaximal finger flexion
contractions (small muscle mass) and fatigue in healthy humans. Study 3 investigated
the effects of digoxin on K+ regulation during progressive increasing intensity
submaximal leg cycling exercise (large muscle mass) and fatigue in the same healthy
participants as in study 2. A secondary focus of this thesis was to examine the ionic,
metabolic and acid-base disturbances during small and large muscle mass exercise
and in recovery. This included the regulatory role of NKA in active (study 1 and 2) and
inactive tissue (study 3), during small (study 1 and 2) and large (study 3) muscle mass
exercise.