The functional relevance of autoantibodies (Abs) against @entity299 ( @entity299 ) in clinical @entity1000 ( @entity384 ) remains controversial. The study sought to determine effects of @entity1 Abs affinity-purified (AF) by immunoaffinity column chromotography on excitation-contraction coupling in isolated myocytes. Effects of @entity299 -Abs from @entity712 @entity1 with @entity384 (n=19) and @entity741 ( @entity741 , n=19) on contractility, L-type @entity141 current, and @entity141 transients in continuously perfused @entity35 ventricular myocytes were studied. Immunofluorescence studies using confocal microscopy were carried out to determine whether Abs were internalized. AF-Abs from either group did not differ in IgG titer but differed in their elution profiles. The @entity3172 subclass response was higher in AF fractions from @entity384 (21%) than @entity741 (5%) @entity1 . The Abs reduced the capacity of field-stimulated myocytes to contract in a dose-dependent manner. Inhibition of contraction, as a percentage of untreated cells, was greater with @entity384 than @entity741 -Abs (P=0.004), and the effect was independent of Ab titer. An increase in frequency of the beating myocytes (0.2 to 3.0 Hz) raised peak systolic and diastolic levels of [ @entity141 ]i of cells treated with @entity384 but not @entity741 -Abs (P<0.005). The AF-Abs were not internalized by myocytes and had no effect on L-type @entity141 currents. The altered sensitivity of the myofilaments to [ @entity141 ]i by @entity299 -Abs may represent a potential mechanism of autoantibody-mediated impairment in clinical @entity384 .

XXXX @entity299 autoantibodies impair myocyte contractility: a cause-and-effect relationship.

@entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity712 :: ('MESH:D006333', 'Disease') :: ['heart failure'] @entity3172 :: ('3502', 'Gene') :: ['IgG3'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity384 :: ('MESH:D002311', 'Disease') :: ['DCM'] @entity1000 :: ('MESH:C536277', 'Disease') :: ['idiopathic dilated cardiomyopathy'] @entity741 :: ('MESH:D017202', 'Disease') :: ['IHD', 'ischemic heart disease'] @entity299 :: ('MESH:D006331', 'Disease') :: ['CM', 'cardiac myosin'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca2+']
@entity1 :: (9606,Species) :: ['Human']
