Abstract 18376: Ethanol Induces Prolongation of the Plateau Phase of Acetylcholine-Activated K+ Current in Mouse Atrial Cardiomyocytes
Ethanol exerts biological effects through multiple receptors, including ion channels. Alcohol intoxication may induce atrial fibrillation prone cellular electrophysiological changes and arrhythmias, primarily AF. Modifications of inward rectifier potassium currents have been implicated in the pathogenesis of AF. However, the mechanisms underlying the potential association between acute ethanol exposure and AF remain unclear. Therefore, we hypothesized that alcohol may affect acetylcholine-activated K+ current in atrial cardiomyocytes.
Methods: IKACh current was recorded using a nystatin-perforated whole cell patch-clamp technique following activation by ACh. After the measurement of baseline IKACh current, cardiomyocytes were exposed to ethanol (100 mM for 10 min) and IKACh current was re-measured. Current-voltage (I-V) curves were obtained from the current response induced by voltage ramps between –120 and +60 mV from the holding potential of –40 mV.
Results: Application of ACh (10 μM) to the bath solution promptly activated IKACh in cardiomyocytes. After switching the bath solution to an ethanol mixed solution, IKACh desensitization was attenuated and the plateau phase (quasi-steady-state) of IKACh current was prolonged. The ethanol-induced prolongation of the plateau phase was slowly decreased 4-5 minutes thereafter. The amplitude of IKACh upon second exposure to ACh was similar to that upon initial exposure. The Current-voltage curve in the presence of ethanol was significantly larger than that in the presence of ACh. In addition, tertiapin-q inhibited the activation of IKACh current as well as plateau phase prolongation by ethanol, while atropine did not.
Conclusion: Our results indicated that ethanol prolongs the duration of the plateau phase of ACh-activated K+ current. This is the first study demonstrating the effects of ethanol on atrial IKACh, which could explain the mechanism of AF initiation resulting from heavy alcohol drinking.
Author Disclosures: T. Cha: None. E. Choi: None. G. Yu: None. B. Kim: None. D. Park: None.
- © 2016 by American Heart Association, Inc.