Abstract
The electrophysiological properties of pulmonary vein (PV)‐cardiomyocytes, and their responses to the sympathetic neurotransmitter, noradrenaline (NA), are thought to differ from those of the left atrium (LA) and contribute to atrial ectopy. The aim of this study was to examine rat PV cardiomyocyte electrophysiology and responses to NA in comparison with LA cells. LA and PV cardiomyocytes were isolated from adult male Wistar rat hearts, and membrane potentials and ion currents recorded at 36°C using whole‐cell patch‐clamp techniques. PV and LA cardiomyocytes did not differ in size. In control, there were no differences between the two cell‐types in zero‐current potential or action potential duration (APD) at 1 Hz, although the incidence of early afterdepolarizations (EADs) was greater in PV than LA cardiomyocytes. The L‐type Ca2+ current (I CaL) was ~×1.5 smaller (p = .0029, Student's t test) and the steady‐state K+ current (I Kss) was ~×1.4 larger (p = .0028, Student's t test) in PV than in LA cardiomyocytes. PV cardiomyocyte inward‐rectifier current (I K1) was slightly smaller than LA cardiomyocyte I K1. In LA cardiomyocytes, NA significantly prolonged APD30. In PV cells, APD30 responses to 1 μM NA were heterogeneous: while the mean percentage change in APD30 was not different from 0 (16.5 ± 9.7%, n cells/N animals = 12/10, p = .1177, one‐sample t test), three cells showed shortening (‐18.8 ± 6.0%) whereas nine showed prolongation (28.3 ± 10.1%, p = .008, Student's t test). NA had no effect on I K1 in either cell‐type but inhibited PV I Kss by 41.9 ± 4.1% (n/N = 23/11 p < .0001), similar to LA cells. NA increased I CaL in most PV cardiomyocytes (median × 2.2‐increase, p < .0001, n/N = 32/14, Wilcoxon‐signed‐rank test), although in 7/32 PV cells I CaL was decreased following NA. PV cardiomyocytes differ from LA cells and respond heterogeneously to NA.
Highlights
Atrial fibrillation (AF) is a rapid and irregular activation of the atria that can lead to serious clinical consequences, including reduced left ventricular function, irregular ventricular rhythm, heart failure, and stroke, and is associated with a significantly elevated risk of death (Camm et al, 2010)
It has been suggested that the lower background K+ conductance, more depolarized resting membrane potential and shorter action potential duration (APD) of pulmonary vein (PV) cardiomyocytes compared to left atrium (LA) cardiomyocytes, together with differences in fiber orientation in the vicinity of the PVs, may render this region more susceptible to abnormal automaticity, triggered activity and reentry (Chen & Chen, 2006; Ehrlich et al, 2003; Nattel, 2003)
While the standard deviations of NA-induced percentage changes in APD30 were similar in LA (42.4%) and PV (33.8%) cardiomyocytes, the greater heterogeneity of PV compared with LA cardiomyocytes in responses to NA was evident in the greater coefficient of variation (CoVs) in PV cells (204.1, n/N = 12/10) compared with LA cells (72.0, n/N = 8/5; p = .0008)
Summary
Atrial fibrillation (AF) is a rapid and irregular activation of the atria that can lead to serious clinical consequences, including reduced left ventricular function, irregular ventricular rhythm, heart failure, and stroke, and is associated with a significantly elevated risk of death (Camm et al, 2010). Isolation of the PVs from the LA by catheter ablation has been shown to be effective in restoring and maintaining SR in AF patients (Oral et al, 2006; Pappone et al, 2006). It has been suggested that the lower background K+ conductance, more depolarized resting membrane potential and shorter action potential duration (APD) of PV cardiomyocytes compared to LA cardiomyocytes, together with differences in fiber orientation in the vicinity of the PVs, may render this region more susceptible to abnormal automaticity, triggered activity and reentry (Chen & Chen, 2006; Ehrlich et al, 2003; Nattel, 2003). The objective of this study was to characterize the electrophysiological properties of isolated PV cardiomyocytes and their responses to NA in comparison with LA cardiomyocytes from rat hearts
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