Altered phosphorylation and calcium sensitivity of cardiac myofibrillar proteins during sepsis

Altered phosphorylation and Ca2+ sensitivity of cardiac myofibrillar protei ns during different phases of sepsis were investigated. Sepsis was induced by cecal ligation and puncture (CLP). The results show that phosphorylation of troponin I (TnI) was increased by 268% during the early phase (9 h afte r CLP) but decreased by 46% during the late phase (18 h after CLP) of sepsi s. Phosphorylation of C protein was increased by 76% during the early phase but decreased by 41% during the late phase of sepsis. Phosphorylation of m yosin light chain-2 (MLC-2) remained unaltered during the early phase but w as decreased by 38% during the late phase of sepsis. Phosphorylation of TnT was unaffected during the progression of sepsis. The increases in the phos phorylation of TnI and C protein during early sepsis were associated with t he decrease in the Ca2+ sensitivity of myofilaments and the increases in my ocardial changes in tension development (+dP/dt(max)) and cAMP level. The d ecreases in the phosphorylation of TnI and C protein during late sepsis coi ncided with the declines in the activities of myofibrillar ATPase, Ca2+ sen sitivity of myofilaments, myocardial +dP/dt(max), and cAMP content. The inc reases and the decreases in the phosphorylation of TnI and C protein, +dP/d t(max), and the tissue cAMP level were sensitive to isoproterenol stimulati on and propranolol inhibition. These findings suggest that alterations in t he phosphorylation of myofibrillar proteins, such as TnI, C protein, and ML C-2, and changes in the activities and the Ca2+ sensitivity of myofibrillar ATPase may contribute to the altered cardiac function during the progressi on of sepsis. Furthermore, the sepsis-induced alterations in the phosphoryl ation and Ca2+ sensitivity of cardiac myofibrillar proteins were mediated v ia a beta -adrenergic receptor pathway.