Dynamics and Consequences of Potassium Shifts in Skeletal Muscle and Heart During Exercise

Abstract

Since it became clear that K(+) shifts with exercise are extensive and can cause more than a doubling of the extracellular [K(+)] ([K(+)](s)) as reviewed here, it has been suggested that these shifts may cause fatigue through the effect on muscle excitability and action potentials (AP). The cause of the K(+) shifts is a transient or long-lasting mismatch between outward repolarizing K(+) currents and K(+) influx carried by the Na(+)-K(+) pump. Several factors modify the effect of raised [K(+)](s) during exercise on membrane potential (E(m)) and force production. 1) Membrane conductance to K(+) is variable and controlled by various K(+) channels. Low relative K(+) conductance will reduce the contribution of [K(+)](s) to the E(m). In addition, high Cl(-) conductance may stabilize the E(m) during brief periods of large K(+) shifts. 2) The Na(+)-K(+) pump contributes with a hyperpolarizing current. 3) Cell swelling accompanies muscle contractions especially in fast-twitch muscle, although little in the heart. This will contribute considerably to the lowering of intracellular [K(+)] ([K(+)](c)) and will attenuate the exercise-induced rise of intracellular [Na(+)] ([Na(+)](c)). 4) The rise of [Na(+)](c) is sufficient to activate the Na(+)-K(+) pump to completely compensate increased K(+) release in the heart, yet not in skeletal muscle. In skeletal muscle there is strong evidence for control of pump activity not only through hormones, but through a hitherto unidentified mechanism. 5) Ionic shifts within the skeletal muscle t tubules and in the heart in extracellular clefts may markedly affect excitation-contraction coupling. 6) Age and state of training together with nutritional state modify muscle K(+) content and the abundance of Na(+)-K(+) pumps. We conclude that despite modifying factors coming into play during muscle activity, the K(+) shifts with high-intensity exercise may contribute substantially to fatigue in skeletal muscle, whereas in the heart, except during ischemia, the K(+) balance is controlled much more effectively.

Salbutamol effects on systemic potassium dynamics during and following intense continuous and intermittent exercise

“…Potassium clearance during exercise also occurs via uptake by other non-contracting or relatively inactive muscles, and also splanchnic K + uptake (Lindinger 1995;Sejersted and Sjøgaard 2000;Clausen 2003 (Hostrup et al 2014a;Collomp et al 2000;Grove et al 1995;Newnham et al 1993;Van Baak et al 2000), or in samples drawn only after completion of, rather than during exercise (Hostrup et al 2014a;Kalsen et al 2014;Hostrup et al 2014b;Larsson et al 1997;Grove et al 1995); and/or utilised oral salbutamol (Collomp et al 2000;Van Baak et al 2000;Hostrup et al 2014a;Goubault et al 2001 after prolonged cycling to exhaustion (Van Baak et al 2000), or at 5-10 min recovery after repeated 30 s sprints or repeated bouts of high intensity cycling, although greater reductions were evident at 1 or 2 min after some individual bouts (Hostrup et al 2014a). Similarly, after salbutamol inhalation (800 µg), there was no further change in antecubital venous [K + ] at 2-10 min after exhaustive cycling at 85% VO 2peak (Goubault et al 2001).…”

“…Salbutamol typically does not enhance performance during endurance exercise (Koch et al 2015;Pluim et al 2011), when K + disturbances are modest (Sejersted and Sjøgaard 2000), with some exceptions, where venous [K + ] was also reduced by ~0.2-0.4 mM (Van Baak et al 2000;Collomp et al 2000). Performance during a 30 s cycle sprint was enhanced by oral salbutamol (4-8 mg) (Le Panse et al 2007;Collomp et al 2005;Hostrup et al 2014a), with the post-exercise antecubital (Hostrup et al 2014a (Kalsen et al 2014).…”

“…Marked K + shifts occur from intracellular to extracellular fluid in contracting muscles and then into plasma; rapid and precise control of these K + shifts is essential for maintaining muscle excitability and is regulated by the Na + ,K + -ATPase (Na + ,K + -pump, NKA) and other K + transport proteins in skeletal muscle (Clausen 2013b;McKenna et al 2008;Sejersted and Sjøgaard 2000;McDonough and Youn 2005;Clausen 2013a). Pronounced increases in circulating catecholamines occur during intense exercise (Kjaer 1989), which activate NKA in skeletal muscle (Clausen 2003 (Hallen et al 1996).…”

“…Firstly, interpretation is difficult from studies measuring only antecubital venous [K + ] (Hostrup et al 2014a;Collomp et al 2000;Grove et al 1995;Newnham et al 1993;Van Baak et al 2000), as this can underestimate arterial [K + ] by as much as 2 mM during intense exercise, due to substantial K + clearance by forearm muscles (Lindinger 1995;McKenna et al 1997;Lindinger et al 1995;Kowalchuk et al 1988). Secondly, numerous studies measured [K + ] in blood drawn only after completion of exercise (Hostrup et al 2014a;Kalsen et al 2014;Larsson et al 1997;Grove et al 1995;Hostrup et al 2014b), when plasma [K + ] is falling precipitously (McKenna et al 1997;Sejersted and Sjøgaard 2000). Nonetheless, despite these limitations, there is evidence suggesting salbutamol may affect both K + dynamics and performance under certain conditions.…”

Mechanisms of exercise-induced muscle damage and fatigue: Intracellular calcium accumulation

“…Pursuant to this consideration, and to more closely approach physiological conditions, Allen et al 16) investigated intracellular phosphate concentration ([P(i)]), measured by (31)P nuclear magnetic resonance (NMR) and myoplasmic and sarcoplasmic reticulum (SR) calcium concentrations during tetanic contractions, in in vivo mouse skeletal muscle. They showed that the initial phase of muscle fatigue is accompanied by a rise in [P(i)] and a decrease in tetanic myoplasmic calcium -a very different scenario from that observed in vitro 24,76,83,84) . Thus, a compelling case may be made for studying the mechanisms of muscle fatigue in vivo using contemporary models as and when they become available.…”