G015 Adrenergic regulation of the resting membrane potential in the left atrium and thoracic veins of the rat

Abstract

The physiology of cardiac muscle in thoracic veins is of interest as a source of ectopic activity which can lead to paroxystic atrial fibrillation (Haissaguerre et al. 1998 N Engl J Med 339: 659-666 ; Chen et al. 1999 Circulation 100:1879-1886). We have shown that noradrenalin can induce automatic ectopic activity in the pulmonary vein of the rat (Maupoil et al. 2007 Br J Pharmacol 150:899-905). Here we describe the effects of adrenergic agonists upon the resting membrane potential recorded with intracellular microelectrodes from cardiac muscle in the left atrium (LA), pulmonary veins (PV) and superior vena cava (SVC) of the rat. Isolated tissues were continuously perfused with Krebs-Heinseleit solution aerated with 95 % O2, 5 % CO2 and maintained at 36-37 °C. The quiescent resting membrane potentials were: LA −84±1 mV (n=14), SVC −74±1 mV (n=14), PV −69±1 mV (n=17). In each tissue noradrenalin (10-5M) induced a biphasic response with an initial hyperpolarisation (LA −3±1 mV, SVC −9±1 mV, PV −8±1 mV) followed by a depolarisation (LA +1±2 mV, SVC +15±2 mV, PV +34±1 mV). Only in PV did noradrenalin induce automatic electrical activity when the membrane potential reached ∼−50 mV. The α-adrenergic agonist cirazoline (10-6M) induced a monophasic depolarisation of the resting membrane potential in each tissue: to −80±2 mV in LA, to −49±1 mV in SVC and to −34±1 mV in PV. In no case did cirazoline induce automatic electrical activity. The β-adrenergic agonist isoprenaline (10-7M) induced a monophasic hyperpolarisation of the resting membrane potential in each tissue: to −87±1 mV in LA, to −79±2 mV in SVC and to −80±2 mV in PV. 1. There are significant differences between the resting membrane potentials of the left atrium and both thoracic veins. 2. The responses of the resting membrane potential to adrenergic stimulation are qualitatively similar but quantitatively different with LA < SVC < PV. 3. Depolarisation is not sufficient to induce automatic electrical activity.