{'fraction_non_alphanumeric': 0.03872129671319226, 'fraction_numerical': 0.013957676722197209, 'mean_word_length': 5.121212121212121, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Is interstitial K+ accumulation a key factor in the fatigue process under physiological conditions?

Muscle fatigue, i.e. the decrease in muscle force in response to prolonged or repeated contractions, can originate from any impairment along the neuromuscular system, from a reduction in central neural drive to impaired contractile protein interaction. At the muscle level, a decrease in the force-generating capacity can result from (i) an impaired force per cross-bridge, (ii) a reduced myofibrillar Ca2+ sensitivity and (iii) a decreased Ca2+ release from the sarcoplasmic reticulum (SR). During prolonged activity, the interstitial K+ increases and concentrations of 10–12 mm have been observed. Therefore, resultant sarcolemmal excitability, leading to a reduction in the amplitude of the action potential, can result in impaired SR Ca2+ release. This last factor was the point of interest in a recent article in The Journal of Physiology by Clausen & Nielsen (2007), that investigated the effect of excitability failure on force production during fatigue of rat soleus muscle exposed to different bath K+ concentrations ([K+]o). Clausen & Nielsen showed that the rate of force decline was greater when muscle was pre-exposed for 10–40 min to a high [K+]o (10 mm) and then electrically stimulated compared with low [K+]o (4 mm). They also showed that this increased fatigability could be counteracted by applying different agents known to directly or indirectly stimulate the Na+–K+ pumps. Thus, the data obtained by Clausen & Nielsen (2007) strongly indicate that these high [K+]o values induce a reduction in sarcolemmal excitability, leading to a decrease in soleus endurance which can be prevented by the stimulation of the Na+–K+ pump. 
 
Nevertheless, it is possible that these results are confined to the experimental conditions used to induce fatigue. In their study, Clausen & Nielsen (2007) stimulated soleus muscle continuously at 60 Hz for 1 min; muscle endurance was then assessed by calculating the rate of force decline over the first 20 s of stimulation. In this letter, the possibility that a rise in [K+]o may not be a critical factor of muscle fatigue under physiological conditions is discussed.