title: Hypoxia/fatigue-induced degradation of troponin I and troponin C: new insights into physiologic muscle fatigue.
abstract: Conditions such as respiratory failure and cardiopulmonary arrest can expose the diaphragm to hypoxemia. In skeletal muscles, fatiguing stimulation renders muscles hypoxic, which has long been known to dramatically reduce muscle function. We have previously demonstrated that fatiguing stimulation under hypoxic conditions disrupts both the excitation-contraction coupling (ECC) process and the isometric contractile properties (ICP) in intact diaphragm muscle strips and the contractile properties of skinned fibers isolated from these muscles. Here we have analyzed the effects of intermittent fatiguing stimulation on specific muscle proteins in muscle strips from mouse diaphragms that have been exposed to hypoxia. We report for the first time that the effects of hypoxia-fatigue, namely to decrease maximal tetanic force, maximal calcium-activated force and calcium sensitivity of the mouse diaphragm muscle, are associated with the degradation of troponins TnI and TnC (Western blot analysis). The concentrations of TnT and actin did not change under these same conditions. Because troponins are integrally involved in regulating the interaction between actin and myosin during the cross-bridge cycle, the degradation of TnI and TnC may explain the effects of hypoxia-fatigue on the ICP. This interpretation is supported by the observations that extraction of troponins from control skinned fibers mimics the effects of hypoxia-fatigue on contractile function and that incorporation of native troponins into fibers isolated from hypoxic-fatigued muscles partially restores function.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: M
authors.initials: M
authors.lastname: de Paula Brotto
authors.forename: S A
authors.initials: SA
authors.lastname: van Leyen
authors.forename: L S
authors.initials: LS
authors.lastname: Brotto
authors.forename: J P
authors.initials: JP
authors.lastname: Jin
authors.forename: C M
authors.initials: CM
authors.lastname: Nosek
authors.forename: T M
authors.initials: TM
authors.lastname: Nosek
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D004558:Electric Stimulation; D015151:Immunoblotting; D066298:In Vitro Techniques; D051379:Mice; D009119:Muscle Contraction; D018763:Muscle Fatigue / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D019209:Troponin C / Q000737:chemistry / Q000378:metabolism*; D019210:Troponin I / Q000737:chemistry / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D019209:Troponin C; D019210:Troponin I