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