Sejersted OM & Sjøgaard G (2000). Physiol Rev 80, 1411-1481.
University of Heidelberg (2006) Proc Physiol Soc 4, PC4
Poster Communications: Torben Clausen1, Ole B. Nielsen1
1. Physiology , University of Aarhus, Århus, Denmark.
During contractile activity, muscle cells often undergo a net loss of K+, leading to increased interstitial concentration of K+, depolarization and loss of excitability. For almost 70 years, it has repeatedly been proposed that this sequence of events might be an important cause of fatigue (Sejersted & Sjøgaard, 2000). Objections to this idea are that during work, interstitial K+ may not increase sufficiently to elicit inhibition of contractions. Moreover, recent studies on intact mouse muscles failed to detect any inhibitory effect of exposure to 10 mM K+ (Zhang et al. 2006). We have therefore examined this hypothesis by measuring force development in intact soleus muscles. Muscles prepared post mortem from 4-week-old Wistar rats were incubated in oxygenated Krebs-Ringer bicarbonate buffer (30°C) containing K+ in the physiological range (4-10 mM). Immediate increase from 4 to 10 mM K+ caused no significant change in initial force or subsequent force decline seen during continuous stimulation with 0.2 ms 10 V pulses at 60 Hz at 30°C. However, following 20 min of exposure to 10 mM K+, the rate of force decline increased by 618% in comparison to the values recorded at 4 mM K+ (n = 14 vs 8, P < 0.001, unpaired t test). Twenty minutes of exposure to 8 mM K+ increased the rate of force decline by 135% (n = 8 vs 8, P < 0.001). Following return to 4 mM K+, the inhibitory effect of elevated K+ was completely reversible. Since a rise in interstitial K+ can be counteracted by stimulating the Na+-K+ pumps, we examined agents known to exert such an action. The beta2-agonist salbutamol, adrenaline, rat calcitonin gene related peptide (rCGRP) and insulin, when added to the K+-enriched buffers, all induced a highly significant or complete restoration of contractile endurance to the level obtained at 4 mM K+. When the Na+-K+ pumps were activated by intermittent stimulation (1 s 60 Hz trains of 0.2 ms 10 V pulses every 2 min for 20 min before the fatiguing stimulation), contractile endurance was improved by 151% (n = 6 vs 8, P < 0.001). In conclusion, exposure of muscles to elevated [K+]o for sufficient time (20 min) to allow access of K+ to the interstitial water space, leads to marked but reversible inhibition of contractile performance. This effect shows progressive increase with the K+ concentration. Stimulation of the Na+-K+ pumps counteracts or alleviates this inhibition, indicating that muscle fatiguability depends on the balance between excitation-induced rise in [K+]o and clearance of this K+ via the Na+-K+ pumps.
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