Ion currents, action potentials, and noradrenergic responses in rat pulmonary vein and left atrial cardiomyocytes

• Main Authors: Richard C. Bond, Stéphanie C. Choisy, Simon M. Bryant, Jules C. Hancox, Andrew F. James
• Format: Article
• Language: English
• Published: Wiley 2020-05-01
• Series: Physiological Reports
• Subjects: action potential; delayed afterdepolarization; early afterdepolarization; inward‐rectifier K+ current (IK1); L‐type Ca2+ current (ICaL); noradrenaline
• Online Access: https://doi.org/10.14814/phy2.14432

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 (ICaL) was ~×1.5 smaller (p = .0029, Student's t test) and the steady‐state K+ current (IKss) was ~×1.4 larger (p = .0028, Student's t test) in PV than in LA cardiomyocytes. PV cardiomyocyte inward‐rectifier current (IK1) was slightly smaller than LA cardiomyocyte IK1. 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 IK1 in either cell‐type but inhibited PV IKss by 41.9 ± 4.1% (n/N = 23/11 p < .0001), similar to LA cells. NA increased ICaL in most PV cardiomyocytes (median × 2.2‐increase, p < .0001, n/N = 32/14, Wilcoxon‐signed‐rank test), although in 7/32 PV cells ICaL was decreased following NA. PV cardiomyocytes differ from LA cells and respond heterogeneously to NA.