The mechanisms of the negative inotropic effects of autoantibodies against β 3 ‐adrenoceptor in patients with dilated cardiomyopathy on isolated cardiomyocytes

We have previously found that autoantibodies against the second extracellular loop of β 3 ‐adrenoceptor(β 3 ‐AR) from the sera of patients with dilated cardiomyopathy(DCM) have negative effects on cardiomyocytes, here we explored the possible mechanism involved. The anti‐β 3 ‐AR autoantibodies(0.1μmol/L) decreased the peak systolic [Ca 2+ ] iT from 48.54±12.41% of controlto 10.83±3.34% (p<0.001,n=10)in isolated rat cardiomyocytes, which was more significant than specific β 3 ‐AR agonist BRL37344(0.1μmol/L) (17.14±10.81%,p<0.05); Compatible to control group,the autoantibodies(0.1μmol/L)reduced the L‐type calcium current(626±138pA) and potassium current(I K ) (103±52pA) of guinea pig cardiomyocytes (p<0.001,n=10) which was in the same way as the effects induced by BRL37344(0.1μmol/L). Our results demonstrated that the negative inotropic effect on cardiomyocytes of the anti‐β 3 ‐AR autoantibodies was accompanied by a decreased intracellular Ca 2+ transient and reduction of membrane L‐type Ca 2+ current (I CaL ) and delayed rectifier potassium current (I K ) via stimulation of cardiac β 3 ‐adrenoceptor (β 3 ‐AR) without desensitization.