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1 Zoology, La Trobe University, Bundoora, Victoria, Australia
* To whom correspondence should be addressed. E-mail: t.dutka{at}latrobe.edu.au.
When muscle fibers are repeatedly stimulated they may become depolarized and force output decline. Excitation of the transverse-tubular (T-) system is critical for activation, but its role in muscle fatigue is poorly understood. Here, mechanically-skinned fibers from rat fast-twitch muscle were used because the sarcolemma is absent but the T-system retains normal excitability and its properties can be studied in isolation. The T-system membrane was fully polarized by bathing the skinned fiber in an internal solution with 126 mM K+ (control solution) or set at partially depolarised levels (~-63 mV and -58 mV) in solutions with 66 or 55 mM K+ respectively, and action potentials (APs) triggered in the sealed T-system by field stimulation. Prolonged depolarization of the T-system reduced tetanic force proportionately more than twitch force, with greater effect at higher stimulation frequency (responses at 20 Hz and 100 Hz reduced to 71 and 62 % in 66 mM K+, and to 54 and 35 % in 55 mM K+, respectively). Double pulse stimulation showed that depolarization increased the repriming period (estimated minimum time before a second AP can be produced) from ~4 ms to ~7.5 and 15 ms in the 66 and 55 mM K+ solutions respectively. These results demonstrate that T-system depolarization reduces tetanic force by impairing AP repriming, rather than by preventing AP generation per se or by inactivating the T-system voltage-sensors. The findings also explain why it is advantageous to reduce the rate of motoneuron stimulation to muscles during repeated or prolonged periods of activity.
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