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Ex Vivo Assessment of Contractility, Fatigability and Alternans in Isolated Skeletal Muscles
Published on: November 1, 2012
Evidence that the Na+-K+ leak/pump ratio contributes to the difference in endurance between fast- and slow-twitch
T Clausen1, K Overgaard, O B Nielsen
1Department of Physiology, University of Aarhus, Arhus, Denmark.
Aim:
Muscles containing predominantly fast-twitch (type II) fibres [ext. dig. longus (EDL)] show considerably lower contractile endurance than muscles containing mainly slow-twitch (type I) fibres (soleus). To assess whether differences in Na+-K+ fluxes and excitability might contribute to this phenomenon, we compared excitation-induced Na+-K+ leaks, Na+ channels, Na+-K+ pump capacity, force and compound action potentials (M-waves) in rat EDL and soleus muscles.
Methods:
Isolated muscles were mounted for isometric contractions in Krebs-Ringer bicarbonate buffer and exposed to direct or indirect continuous or intermittent electrical stimulation. The time-course of force decline and concomitant changes in Na+-K+ exchange and M-waves were recorded.
Results:
During continuous stimulation at 60-120 Hz, EDL showed around fivefold faster rate of force decline than soleus. This was associated with a faster loss of excitability as estimated from the area and amplitude of the M-waves. The net uptake of Na+ and the release of K+ per action potential were respectively 6.5- and 6.6-fold larger in EDL than in soleus, which may in part be due to the larger content of Na+ channels in EDL. During intermittent stimulation with 1 s 60 Hz pulse trains, EDL showed eightfold faster rate of force decline than soleus.
Conclusion:
The considerably lower contractile endurance of fast-twitch compared with slow-twitch muscles reflects differences in the rate of excitation-induced loss of excitability. This is attributed to the much larger excitation-induced Na+ influx and K+ efflux, leading to a faster rise in [K+]o in fast-twitch muscles. This may only be partly compensated by the concomitant activation of the Na+-K+ pumps, in particular in fibres showing large passive Na+-K+ leaks or reduced content of Na+-K+ pumps. Thus, endurance depends on the leak/pump ratio for Na+ and K+.
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