Mechanism of the exercise hyperkalemia: an alternate hypothesis

Wasserman, Karlman, William W. Stringer, Richard Casaburi,and Yong-Yu Zhang. Mechanism of the exercisehyperkalemia: an alternate hypothesis. J. Appl.Physiol. 83(2): 631-643, 1997.A progressivehyperkalemia is observed as exercise intensity increases. The currentmost popular hypothesis for the hyperkalemia is that theNa⁺-K⁺pump cannot keep pace with the K⁺efflux from muscle during the depolarization-repolarization process ofthe sarcolemmal membrane during muscle contraction. In this report, wepresent data that suggest an alternate hypothesis to those previouslydescribed. Because phosphocreatine (PCr) is a highly dissociated acidand creatine is neutral at cell pH, the concentration of nondiffusibleanions decreases, and an alkaline reaction takes place when PCrhydrolyzes. This creates a state of cation(K⁺) excess andH⁺ depletion in the cell. Toexamine the balance of K⁺ andH⁺ for exercising muscle duringthe early period of exercise when PCr changes most rapidly, catheterswere inserted into the brachial artery and femoral vein (FV) in fivehealthy subjects who performed two 6-min cycle ergometer exercise testsat 40 and 85% of peak oxygen uptake. FV blood was sampled every 5 sduring the first 2 min, then every 30 s for the remaining 4 min ofexercise and the first 3 min of recovery, and then less frequently forthe next 12 min. Arterial sampling was every 30 s during exercise andsimultaneous with FV sampling during recovery. ArterialK⁺ concentration(K⁺]) increase laggedFV K⁺]increase. The hyperkalemia observed during early exerciseresults from K⁺ release fromskeletal muscle. FVK⁺] increased by 5 sof the start of exercise and followed the rate ofH⁺ loss from the FV blood for thefirst 30 s of exercise. FV lactate andNa⁺ kinetics differed fromK⁺ kinetics during exercise andrecovery. As predicted from the PCr hydrolysis reaction, the exercisinglimb took up H⁺ and releasedK⁺ at the start of exercise (first30 s) at both exercise intensities, resulting in a FV metabolicalkalosis. K⁺ release wasessentially complete by 3 min, the time at which oxygen uptake (and,presumably, PCr) reached its asymptote. These findings lead us tohypothesize that the early K⁺release by the cell takes place withH⁺ exchange and that the majormechanism for the exercise hyperkalemia is the reduction innondiffusible intracellular anions in the myocyte as PCr hydrolyzes.