β1-Adrenoceptor Autoantibodies Affect Action Potential Duration and Delayed Rectifier Potassium Currents in Guinea Pigs

Abstract

β1-Adrenoceptor autoantibodies (β1-AAs) affect the action potential duration (APD) in cardiomyocytes and are related to ventricular arrhythmias. The delayed rectifier potassium current (I K) plays a crucial role in APD, but the effects of β1-AAs on I K have not been completely illuminated. This work aimed to observe the effects of β1-AAs on I K and APD and further explore the mechanisms of β1-AA-mediated ventricular arrhythmias. β1-AAs were obtained from sera of patients with coronary heart disease (CHD) and nonsustained ventricular tachycardia. With whole-cell patch clamp technique, action potentials and I K were recorded. The results illustrated 0.1 μmol/L β1-AAs shortened APD at 50 % (APD50) and 90 % (APD90) of the repolarization. However, at 0.01 μmol/L, β1-AAs had no effects on either APD90 or APD50 (P > 0.05). At 0.001 μmol/L, β1-AAs significantly prolonged APD90 and APD50. Moreover, β1-AAs (0.001, 0.01, 0.1 μmol/L) dose-dependently increased the rapidly activating delayed rectifier potassium current (I Kr), but similarly decreased the slowly activating delayed rectifier potassium current (I Ks) and increased L-type calcium currents at the different concentrations. Taken together, the IKr increase induced by high β1-AA concentrations is responsible for a significant APD reduction which would contribute to repolarization changes and trigger the malignant ventricular arrhythmias in CHD patients.

β1‐Adrenoceptor autoantibodies increase the susceptibility to ventricular arrhythmias involving abnormal repolarization in guinea‐pigs

“…Our study confirmed that β 1 ‐AR mAbs prolonged MAPD 90−30 , which may be attributed to increased I Kr and I CaL and decreased I Ks of ventricular myocytes of guinea‐pigs (Zhao et al . ).…”

“…) and I Kr (Zhao et al . ), but decrease I Ks by binding with β 1 ‐AR (Medei et al . ) in the ventricular myocardium.…”

“…We have previously reported that β 1 ‐AAs increased the rapidly activating delayed rectifier K + current ( I Kr ) and L‐type calcium channel current ( I Ca‐L ) and decreased I Ks in the left ventricular myocytes of guinea‐pigs (Zhao et al . ). Moreover, the effects of β 1 ‐AAs on action potential duration (APD) have been observed.…”

“…In our previous research, β 1 ‐AAs at different concentrations adversely affected the APD of ventricular cardiomyocytes in guinea‐pigs (Zhao et al . ).…”

“…Some studies suggest that β 1 ‐AAs may induce ventricular arrhythmias, especially in patients with idiopathic dilated cardiomyopathy (Zhao et al . ) and chronic Chagas disease (Maciel et al . ).…”