EXCITATION-CONTRACTION COUPLING IN NORMAL AND MYOPATHIC HAMSTER HEARTS .3. FUNCTIONAL DEFICIENCIES IN INTERSTITIAL GLYCOPROTEINS

Summary: Extracellular and surface bound Ca is essential to excitation-contraction (E-C) coupling in mammalian cardiac muscle. In intact hearts from cardiomyopathic hamster with congestive heart failure, a concomitant decrease in the Ca content of a superficial pool was associated with the reduced contractility. Ca binding to cardiac sarcolemmal ghosts prepared from these hearts revealed two binding sites by Scatchard plot. In normal hamsters, the low affinity site had a capacity of 114 nmol Ca·mg-1 protein, a KD of 1.5 mmol·litre-1 and was sensitive to neuraminidase treatment but not to 100 mmol·litre-1 Na, K, or Li. Ca binding in vitro approached a 1:1 relationship with the sialic acid content of the ghosts, 159 nmol·mg-1 protein. The activity of the enzyme responsible for glycosidically linking sialic acid to interstitial and sarcolemmal glycoproteins, sialyltransferase, was reduced from 1.80 to 0.41 pmol·mg-1 protein in the myopathic hearts. We suggest the functional defect in the hamster cardiomyopathy is a reduction in sialyltransferase activity leading to the deficiency in surface sialic acid residues. As a consequence, contractility is reduced, but Ca influx is increased. Reflex sympathetic activity increases Ca influx resulting in Ca overload" and eventual cellular necrosis."