Chronotropic effect of stimulation of α1 adrenergic receptors in mouse atria

Major subtypes of α 1 adrenergic receptors (α 1 ARs) are present in heart atria and ventricles in various species including human. Emerging studies have been much focused on the roles of α 1 ARs in cardiac contraction and remodeling but paid little attention to their effects on heart rate (HR). In this study, effects of stimulation of α 1 ARs on HR were observed in isolated mouse atria preparations. Double‐atria preparations were isolated from 1 to 3 months old ICR mice and maintained in 37°C, oxygen bubbled Krebs solution in a tissue chamber. A pair of electrodes was placed on the preparation to record atrial ECG. Treatments with a α 1 AR agonist, phenylephrine (PE), induced a dose‐dependent increase in HR. This positive chronotropic effect was blocked by prazosin, a non‐selective α 1 AR antagonist, and WB 4101, a selective α 1A AR antagonist, but not Rec 15/2615, a selective α 1B AR antagonist. Moreover, this PE‐induced positive chronotropic effect was diminished by an IP 3 receptor blocker, 2‐APB. Additionally, stimulation of α 1 ARs with PE attenuated cholinergic effect on HR in the atrial preparation. Collectively, these data suggest that α 1A ARs via Gq signaling pathway may play an important role in HR regulation, particularly in disease states when β 1 ARs are desensitized by sympatho‐excitation. This work is supported by American Heart Association grant No. 0835256N and NIH grant No. 1R03AG033291.