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(Circulation. 1995;91:2824-2833.)
© 1995 American Heart Association, Inc.

Articles

Characteristics of the ß-Adrenergic Receptor Complex in the Epicardial Border Zone of the 5-Day Infarcted Canine Heart

Susan F. Steinberg, MD; HongLu Zhang, MPH; Elena Pak, BS; Geraldine Pagnotta, BS; Penelope A. Boyden, PhD

From the Departments of Medicine (S.F.S.) and Pharmacology (S.F.S., H.-L.Z., E.P., G.P., P.A.B.), Columbia University, New York, NY.

Correspondence to Susan F. Steinberg, MD, Department of Pharmacology, Columbia University, College of Physicians and Surgeons, 630 West 168 St, New York, NY 10032.

Background The effect of isoproterenol on increasing the peak amplitude of the L-type calcium current is reduced in myocytes dispersed from the epicardial border zone (EBZ) of the 5-day infarcted canine heart when compared with control cells from noninfarcted hearts. This suggests that specific alterations in the ß-adrenergic receptor complex develop in this setting. The present study is an examination of individual components of the ß-adrenergic receptor complex with the aim of elucidating the biochemical defect(s) that might be responsible for the diminished ß-adrenergic receptor responsiveness in the myocytes that survive in the infarcted heart.

Methods and Results We compared components of the ß-adrenergic receptor signaling pathway in membranes prepared from the EBZ of the 5-day infarcted heart and a remote, noninfarcted region (RZ) of the same ventricle as well as the corresponding regions of noninfarcted ventricles. Defects in multiple components of the ß-adrenergic receptor complex were confined to the EBZ of the 5-day infarcted heart. These include a decrease in ß-adrenergic receptor density; diminished basal, guanine nucleotide–, isoproterenol-, forskolin-, and manganese-dependent adenylyl cyclase activities; an increase in the EC₅₀ for isoproterenol-dependent activation of adenylyl cyclase; a diminished level of the -subunit of the G_s protein; and an elevated level of the -subunit of the G_i protein.

Conclusions Defects in multiple components of the membrane ß-adrenergic receptor complex were identified in the EBZ of the 5-day infarcted canine heart. This constellation of abnormalities would be predicted to impair functional ß-adrenergic responsiveness and contribute to the defect in isoproterenol-dependent stimulation of the L-type calcium current in myocytes isolated from this tissue.

Key Words: receptors, adrenergic, beta • proteins • adenylyl cyclase • myocardial infarction

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