Abstract 18272: Differential Effects of Carvedilol and Atenolol on Acetylcholine-Activated K+ Current ; Possible Atrial-Specific Antiarrhythmic Effects of Carvedilol on Atrial Fibrillation
Recently, the upregulation of IKACh and muscarinic receptor expression has been reported in atrial fibrillation (AF) patients and in AF induced experimentally in dogs. Therefore blockage of IKACh could terminate AF induced by increased vagal tone. Blockade of atrial-specific K+ channels could provide an approach for the treatment of atrial arrhythmia without adverse ventricular effects. Randomized trials have demonstrated that β blockers have beneficial long-term effects on mortality and morbidity in patients with heart failure. However, not all β blockers have identical effects, and the use of various β blockers in AF has yet to be thoroughly evaluated. Therefore, we examined the effects of carvedilol and atenolol on acetylcholine-activated K+ channels in mouse atrial cardiomyocytes.
Methods: In the present study, IKACh current was recorded using a nystatin-perforated whole cell patch-clamp technique. Mouse atrial cardiomyocytes were voltage clamped at -40 mV, and IKACh was activated by extracellular application of acetylcholine. After the baseline IKACh current was measured, varying concentrations of β blockers were applied for 5 minutes, and a second IKACh current was recorded. Action potential duration (APD) and current-voltage curves were recorded from isolated cardiomyocytes.
Results: The application of acetylcholine (10 μM) to the bath solution activated IKACh in cardiomyocytes. Carvedilol inhibited IKACh in a dose-dependent manner between 0.1 and 5 μM. The concentration required for half-maximal inhibition (IC50) was 1.03 μM for the peak and 1.04 μM for the quasi-steady-state. In addition, carvedilol attenuated acetylcholine-induced APD shortening. We next investigated the effects of atenolol on IKACh using the same experimental protocol. Addition of atenolol to the bath solution did not alter the peak amplitude or quasi-steady-state of the IKACh currents compared to controls.
Conclusion: We found that the β blocker carvedilol suppressed acetylcholine-activated potassium current, while another β blocker, atenolol, did not. Blockade of atrial K+ channels by carvedilol provides another potential option for the treatment of AF. These findings suggest that carvedilol may be used in AF as an atrial-specific antiarrhythmic agent.
Author Disclosures: T. Cha: None. E. Choi: None. G. Yu: None. B. Kim: None. D. Park: None.
- © 2016 by American Heart Association, Inc.