Hypoxemia-induced modification of troponin I and T in canine diaphragm.
Impaired muscle function (fatigue) may result, in part, from modification of contractile proteins due to inadequate O(2) delivery. We hypothesized that severe hypoxemia would modify skeletal troponin I (TnI) and T (TnT), two regulatory contractile proteins, in respiratory muscles. Severe isocapnic hypoxemia (arterial partial pressure of O(2) of approximately 25 Torr) in six pentobarbital sodium-anesthetized spontaneously breathing dogs increased respiratory frequency and electromyographic activity of the diaphragm and internal and external obliques, with death occurring after 131-285 min. Western blot analysis revealed proteolysis of TnI and TnT, 17.5- and 28-kDa fragments, respectively, and higher molecular mass covalent complexes, one of which (42 kDa) contained TnI (or some fragment of it) and probably TnT in the costal and crural diaphragms but not the intercostal or abdominal muscles. These modifications of myofibrillar proteins may provide a molecular basis for contractile dysfunction, including respiratory failure, under conditions of limited O(2) delivery.
Simpson
J A
JA
Department of Physiology, Queen's University, Kingston, Ontario, Canada K7L 3N6.
van Eyk
J E
JE
Iscoe
S
S
D000818:Animals; D015153:Blotting, Western; D003964:Diaphragm / Q000378:metabolism*; D004285:Dogs; D004576:Electromyography; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D009210:Myofibrils / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D012132:Respiratory Muscles / Q000737:chemistry / Q000378:metabolism; D019210:Troponin I / Q000378:metabolism*; D020107:Troponin T / Q000378:metabolism*
D019210:Troponin I; D020107:Troponin T; D010100:Oxygen