Diaphragmatic fatigue is associated with decreased inositol 1,4,5-trisphosphate formation.

The ability of the rat diaphragm to produce inositol 1,4,5-trisphosphate (InsP3) in response to a maximal contractile stimulus was determine in vitro in both fatigued and nonfatigued diaphragms. InsP3 was produced during a maximal contraction of the diaphragm. After inducing fatigue, there was a significant reduction in the production of InsP3 compared with that in nonfatigued muscle. The maximal force generated by the diaphragm was also decreased after fatigue. A significant positive linear correlation was found between the force developed by the diaphragm and the amount of InsP3 liberated.