Mechanism of the exercise hyperkalemia: an alternate hypothesis

A progressive hyperkalemia is observed as exercise intensity increases. The current most popular hypothesis for the hyperkalemia is that the Na+-K+ pump cannot keep pace with the K+ efflux from muscle during the depolarization-repolarization process of the sarcolemmal membrane during muscle contraction. In this report, we present data that suggest an alternate hypothesis to those previously described. Because phosphocreatine (PCr) is a highly dissociated acid and creatine is neutral at cell pH, the concentration of nondiffusible anions decreases, and an alkaline reaction takes place when PCr hydrolyzes. This creates a state of cation (K+) excess and H+ depletion in the cell. To examine the balance of K+ and H+ for exercising muscle during the early period of exercise when PCr changes most rapidly, catheters were inserted into the brachial artery and femoral vein (FV) in five healthy subjects who performed two 6-min cycle ergometer exercise tests at 40 and 85% of peak oxygen uptake. FV blood was sampled every 5 s during the first 2 min, then every 30 s for the remaining 4 min of exercise and the first 3 min of recovery, and then less frequently for the next 12 min. Arterial sampling was every 30 s during exercise and simultaneous with FV sampling during recovery. Arterial K+ concentration ([K+]) increase lagged FV [K+] increase. The hyperkalemia observed during early exercise results from K+ release from skeletal muscle. FV [K+] increased by 5 s of the start of exercise and followed the rate of H+ loss from the FV blood for the first 30 s of exercise. FV lactate and Na+ kinetics differed from K+ kinetics during exercise and recovery. As predicted from the PCr hydrolysis reaction, the exercising limb took up H+ and released K+ at the start of exercise (first 30 s) at both exercise intensities, resulting in a FV metabolic alkalosis. K+ release was essentially complete by 3 min, the time at which oxygen uptake (and, presumably, PCr) reached its asymptote. These findings lead us to hypothesize that the early K+ release by the cell takes place with H+ exchange and that the major mechanism for the exercise hyperkalemia is the reduction in nondiffusible intracellular anions in the myocyte as PCr hydrolyzes.