Reduced Ca2+ transport across sarcolemma but enhanced spontaneous activity in cardiomyocytes isolated from left atrium-pulmonary veins tissue of myopathic hamster

Abstract

BackgroundSeveral lines of evidence point to a particularly important role of the left atrium (LA) in initiating and maintaining atrial fibrillation (AF). This role may be related to the location of pulmonary veins (PVs) in the LA. The aim of the present study was to investigate the action potential (AP) and ionic currents in LA-PV cardiomyocytes isolated from Bio14.6 myopathic Syrian hamsters (36-57 week-old) versus age-matched F1B healthy control hamsters.Methods and ResultsWhole-cell patch-clamp techniques were used to record AP in current-clamp mode and ionic currents in voltage-clamp mode. The results obtained show that in both healthy and myopathic LA-PV tissue spontaneously discharging cardiomyocytes can be found, but they are more numerous in myopathic (9/29) than in healthy hamsters (4/42, p < 0.05 by χ2 analysis). Myopathic myocytes have shorter AP duration (APD) with smaller ICa,L and INCX than the healthy control. The currents ITO, IK, IK1 and ICa,T are not significantly different in myopathic versus healthy cells.ConclusionsOur results indicate that in myopathic Syrian hamsters LA-PV cardiomyocytes are more prone to automatic rhythms. Also, they show altered electrophysiologic properties, which may be due to abnormal Ca2+ channels and may account for contractile dysfunction.

Calcium in the Pathophysiology of Atrial Fibrillation and Heart Failure

“…Increasing intra-atrial pressure, as found in heart failure, accelerates pulmonary vein firing in intact sheep hearts (Kalifa et al, 2003 ). While this increase appears to be mediated by changes in calcium cycling leading to more delayed afterdepolarizations (Chang et al, 2008 ; Loh et al, 2009 ; Lin et al, 2016 ), the cellular changes responsible for this are unclear. While increased levels of circulating B-type natriuretic peptide have been suggested to increase the rate of spontaneous firing due to increased I Ca(L) and I NCX but decreased late I Na (Lin et al, 2016 ), others report an increase in DADs in the setting of heart failure with decreased I Ca(L) and increased late I Na (Chang et al, 2008 ).…”