title: Transverse tubular system depolarization reduces tetanic force in rat skeletal muscle fibers by impairing action potential repriming.
abstract: When muscle fibers are repeatedly stimulated, they may become depolarized and force output decline. Excitation of the transverse tubular system (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 depolarized levels (approximately -63 and -58 mV) in solutions with 66 or 55 mM K(+), respectively, and action potentials (APs) were 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 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 approximately 4 ms to approximately 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.
authors.affiliation: Dept. of Zoology, La Trobe University, Melbourne 3086, Victoria, Australia. t.dutka@latrobe.edu.au
authors.forename: T L
authors.initials: TL
authors.lastname: Dutka
authors.forename: G D
authors.initials: GD
authors.lastname: Lamb
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012519:Sarcoplasmic Reticulum; D013746:Tetany / Q000378:metabolism*; D013997:Time Factors
chemical_list: D011188:Potassium; D002118:Calcium