Catecholaminergic automatic activity in the rat pulmonary vein: electrophysiological differences between cardiac muscle in the left atrium and pulmonary vein

Abstract

Doisne N, Maupoil V, Cosnay P, Findlay I. Catecholaminergic automatic activity in the rat pulmonary vein: electrophysiological differences between cardiac muscle in the left atrium and pulmonary vein. Am J Physiol Heart Circ Physiol 297: H102-H108, 2009. First published May 8, 2009 doi:10.1152/ajpheart.00256.2009.-Ectopic activity in cardiac muscle within pulmonary veins (PVs) is associated with the onset and the maintenance of atrial fibrillation in humans. The mechanism underlying this ectopic activity is unknown. Here we investigate automatic activity generated by catecholaminergic stimulation in the rat PV. Intracellular microelectrodes were used to record electrical activity in isolated strips of rat PV and left atrium (LA). The resting cardiac muscle membrane potential was lower in PV [Ϫ70 Ϯ 1 (SE) mV, n ϭ 8] than in LA (Ϫ85 Ϯ 1 mV, n ϭ 8). No spontaneous activity was recorded in PV or LA under basal conditions. Norepinephrine (10 Ϫ5 M) induced first a hyperpolarization (Ϫ8 Ϯ 1 mV in PV, Ϫ3 Ϯ 1 mV in LA, n ϭ 8 for both) then a slowly developing depolarization (ϩ21 Ϯ 2 mV after 15 min in PV, ϩ1 Ϯ 2 mV in LA) of the resting membrane potential. Automatic activity occurred only in PV; it was triggered at approximately Ϫ50 mV, and it occurred as repetitive bursts of slow action potentials. The diastolic membrane potential increased during a burst and slowly depolarized between bursts. Automatic activity in the PV was blocked by either atenolol or prazosine, and it could be generated with a mixture of cirazoline and isoprenaline. In both tissues, cirazoline (10 Ϫ6 M) induced a depolarization (ϩ37 Ϯ 2 mV in PV, n ϭ 5; ϩ5 Ϯ 1 mV in LA, n ϭ 5), and isoprenaline (10 Ϫ7 M) evoked a hyperpolarization (Ϫ11 Ϯ 3 mV in PV, n ϭ 7; Ϫ3 Ϯ 1 mV in LA, n ϭ 6). The differences in membrane potential and reaction to adrenergic stimulation lead to automatic electrical activity occurring specifically in cardiac muscle in the PV. atrium; norepinephrine; electrophysiology; atrial fibrillation; thoracic veins THE CAUSE OF FOCAL ELECTRICAL activity in myocardial sleeves within the pulmonary veins (6, 14) which can trigger and sustain atrial fibrillation in humans is unknown.A number of themes have been developed to address possible causes of ectopic activity in the pulmonary veins. An attractive but disputed hypothesis is that cardiac muscle in pulmonary veins contains pacemaker cells that would generate spontaneous activity (5, 24). Quantitative surveys of ion channel currents in isolated cardiac myocytes have looked for differences that might account for an increased tendency toward automatic activity in the pulmonary vein (1,12,21). Extensive studies have been made to determine whether cardiac muscle in pulmonary veins is more prone than the left atrium to develop arrhythmogenic phenomena such as early and delayed afterdepolarizations (EADs and DADs) due to differences in Ca 2ϩ handling and/or tachycardia-triggered activity (5, 34). The irregular orientation of cardiac muscle fibers in the pulmonary vein has been suggested to lead t...

Electrical Activity of the Mouse Pulmonary Vein Myocardium

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Activation of Glibenclamide-Sensitive ATP-Sensitive K + Channels During β-Adrenergically Induced Metabolic Stress Produces a Substrate for Atrial Tachyarrhythmia

“…Interestingly, Findlay et al, 33 working with isolated multicellular rat LA and pulmonary vein sleeve preparations, have recently demonstrated a sustained hyperpolarization of the resting membrane potential in response to selective β-adrenoceptor stimulation, consistent with a β-adrenoceptormediated increase in K + -selective background conductance. Moreover, ISO has been reported to shorten APD in LA from normal mice.…”

A TTX‐Sensitive Resting Na+ Permeability Contributes to the Catecholaminergic Automatic Activity in Rat Pulmonary Vein

“…The most obvious difference was that PV cardiac muscle cells had a lower resting membrane potential (RMP). We have previously reported that there was little difference between the action potentials (AP) evoked by electrical stimulation (2 Hz) in the rat PV and LA cardiomyocytes . However, the RMP in the PV rose following the cessation of electrical stimulation to a steady‐state level that was clearly depolarized (‑70 ± 1 mV) compared with the LA (‐85 ± 2 mV), suggesting that PV cardiomyocytes might have a higher basal permeability to Na + .…”