0194 : Functional consequences of -adrenergic receptors activation in the rat pulmonary veins and left atria

Abstract

The role of adrenergic stimulation on pulmonary veins (PV) ectopy and atrial fibrillation initiation is unclear. In the rat, left atrium (LA) and PV cardiomyocytes (CM) have different reactions to α-adrenergic receptor activation. Here, we examine the functional consequences of α-adrenergic receptors activation by cirazoline in rat LA and PV. PV, LA and right and left atria-PV preparations dissected from male Wistar rats were superfused with a physiological solution at 37°C. Electrical conduction within the LA and the PV was recorded with a linear array of 8 extracellular electrodes. Dual intracellular microelectrode recording used a WPI Duo 773 electrometer amplifier. Calcium transients (CaT) were recorded in isolated CM loaded with Fluo-4. Confocal microscopy was used to visualize the distribution of α-adrenergic receptors labeled with BODIPY-prazosin. In PV but not in LA strips stimulated at 0.1Hz, cirazoline induced a concentration-dependent negative inotropic effect (-79±5% at 1μM, p<0.001 vs. basal) that is not reproduced by the PKC activator PDBu (10μM) or blocked by the PKC inhibitor staurosporine (1μM). This was associated with a decrease in CaT amplitude greater in PV than in LA CM (-77±7% vs. –43±12% at 5nM, p<0.05). In right and left atria- PV preparations with a sinusal rate of 288±12 beats/min, conduction of electrical activity was observed both in the LA and the PVs under basal conditions. Cirazoline (30nM-10μM) induced a progressive loss of conduction from the periphery to the base of the PV (~20min) whereas it was maintained in LA. This resulted from the depolarization of the diastolic membrane potential in the PV whereas full over-shooting action potentials were still recorded in LA. Finally, the BODIPY-prazosin labeling reveals differences concerning the distribution of α-adrenergic receptors between PV and LA CM. In conclusion, activation of α-adrenergic receptors results in a functional isolation of the rat PV independent from PKC activation. The author hereby declares no conflict of interest