HYPER- AND HYPOCARDIODYNAMIC STATES ARE ASSOCIATED WITH EXTERNALIZATION AND INTERNALIZATION, RESPECTIVELY, OF α-ADRENERGIC RECEPTORS IN RAT HEART DURING SEPSIS

Alterations in the distribution of α-adrenergic receptors (αARs) in two subcellular organelles, the sarcolemmal membrane and the light vesicle, of rat heart during the progression of sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP). αARs were assayed by using [3H]prazosin binding and photoaffinity labeling with [125I]arylazidoprazosin in combination with polyacrylamide gel electrophoresis. Septic rat hearts exhibit two distinct phases: an initial hypercardiodynamic (9 h after CLP; early sepsis) followed by a hypocardiodynamic (18 h after CLP; late sepsis) phase. [3H]prazosin binding studies show that during early sepsis, the Bmax (maximal binding capacity) was increased by 21.4% in sarcolemma but was decreased by 22.5% in light vesicles, while during late sepsis, the Bmax was decreased by 25.4% in sarcolemma but was increased by 60.8% in light vesicles. The photoaffinity labeling studies revealed three binding peptides with Mr of 77, 68, and 39 kDa. The total binding for the three label peptides during early sepsis was increased by 25.5% in sarcolemma but was decreased by 40% in light vesicles, while during late sepsis, the total binding was decreased by 32.1% in sarcolemma but was increased by 35.8% in light vesicles. These data indicate that αARs in the rat heart were externalized from light vesicles to sarcolemma during early hypercardiodynamic phase while they were internalized from surface membranes to intracellular compartment during late hypocardiodynamic phase of sepsis. Because αARs play an important role in regulating myocardial contractility, an initial externalization followed by internalization of αARs may contribute to the development of the initial hypercardiodynamic and the subsequent hypocardiodynamic states during sepsis.