Premium
The role of elevations in intracellular [Ca2+] in the development of low frequency fatigue in mouse single muscle fibres.
Author(s) -
Chin E R,
Allen D G
Publication year - 1996
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1996.sp021259
Subject(s) - caffeine , stimulation , chemistry , calcium , tetanic stimulation , muscle fatigue , intracellular , skeletal muscle , medicine , duty cycle , endocrinology , biophysics , biochemistry , biology , neuroscience , electromyography , physics , excitatory postsynaptic potential , voltage , receptor , quantum mechanics
1. Intracellular free calcium concentration ([Ca2+]i) and force were measured in isolated single skeletal muscle fibres from mice. The aim was to determine the extent to which elevations in [Ca2+]i during various stimulation protocols affected subsequent muscle performance. 2. A protocol of repeated tetanic stimulation which elevated [Ca2+]i and caused a large decline in force (fatigue) had a [Ca2+]‐time integral of 36.4 +/‐ 8.1 microM s. A protocol of repeated tetani at a lower duty cycle (stimulation) caused only a small decline in force (9‐16%) but elevated the [Ca2+]‐time integral to 16.7 +/‐ 2.8 and 24.9 +/‐ 1.6 microM s in the absence and presence of 10 mM caffeine, respectively. Caffeine alone raised the [Ca2+]‐time integral to 20.3 +/‐ 3.4 microM s. 3. Following the fatigue protocol there was a proportionately greater loss of force at low stimulation frequencies (30 and 50 Hz) compared with high frequencies (100 Hz) which persisted for up to an hour. This pattern of force loss could be attributed to a uniform reduction in [Ca2+]i at all frequencies. Similar effects were observed after elevating [Ca2+]i with the caffeine + stimulation protocol but were not observed after stimulation or caffeine alone. The higher [Ca2+]‐time integrals during the fatigue and caffeine + stimulation protocols suggest that some threshold for [Ca2+]i must be reached before these effects are observed. 4. The reductions in low frequency force induced by the fatigue and caffeine + stimulation protocols were not due to decreased Ca2+ sensitivity or to decreases in maximum force‐generating capacity of the contractile proteins and therefore are due to a failure of Ca2+ release. 5. The Ca(2+)‐activated neutral protease (calpain) inhibitor calpeptin was not effective in preventing the effects of caffeine + stimulation indicating that the reduction in Ca2+ release was not due to calpain‐mediated hydrolysis of the Ca2+ release channel. 6. Our findings indicate that low frequency fatigue results from increases in [Ca2+]i during fatigue and that these elevations in [Ca2+]i activate some process which leads to failure of excitation‐contraction (E‐C) coupling and Ca2+ release.