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Reducing chloride conductance prevents hyperkalaemia-induced loss of twitch force in rat slow-twitch muscle

By Maarten Geert van Emst, Sjoerd Klarenbeek, Arend Schot, Jaap Jan Plomp, Arie Doornenbal and Maria Elisabeth Everts


Exercise-induced loss of skeletal muscle K+ can seriously impede muscle performance through membrane depolarization. Thus far, it has been assumed that the negative equilibrium potential and large membrane conductance of Cl− attenuate the loss of force during hyperkalaemia. We questioned this idea because there is some evidence that Cl− itself can exert a depolarizing influence on membrane potential (Vm). With this study we tried to identify the possible roles played by Cl− during hyperkalaemia. Isolated rat soleus muscles were kept at 25 °C and twitch contractions were evoked by current pulses. Reducing [Cl−]o to 5 mm, prior to introducing 12.5 mm Ko, prevented the otherwise occurring loss of force. Reversing the order of introducing these two solutions revealed an additional effect, i.e. the ongoing hyperkalaemia-related loss of force was sped up tenfold after reducing [Cl−]o. However, hereafter twitch force recovered completely. The recovery of force was absent at [K+]o exceeding 14 mm. In addition, reducing [Cl−]o increased membrane excitability by 24%, as shown by a shift in the relationship between force and current level. Measurements of Vm indicated that the antagonistic effect of reducing [Cl−]o on hyperkalaemia-induced loss of force was due to low-Cl−-induced membrane hyperpolarization. The involvement of specific Cl− conductance was established with 9-anthracene carboxylic acid (9-AC). At 100 μm, 9-AC reduced the loss of force due to hyperkalaemia, while at 200 μm, 9-AC completely prevented loss of force. To study the role of the Na+−K+−2Cl− cotransporter (NKCC1) in this matter, we added 400 μm of the NKCC inhibitor bumetanide to the incubation medium. This did not affect the hyperkalaemia-induced loss of force. We conclude that Cl− exerts a permanent depolarizing influence on Vm. This influence of Cl− on Vm, in combination with a large membrane conductance, can apparently have two different effects on hyperkalaemia-induced loss of force. It might exert a stabilizing influence on force production during short periods of hyperkalaemia, but it can add to the loss of force during prolonged periods of hyperkalaemia

Topics: Research Papers
Publisher: Blackwell Science Inc
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Provided by: PubMed Central
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