Abstract 12446: Impaired Contractile Response to Systolic Calcium Release Contributes to Atrial Hypocontractility in Patients With Persistent Atrial Fibrillation

BackgroundLong standing persistent atrial fibrillation (AF) is associated with impaired atrial Ca signalling, causing remodeling, hypocontractility and ectopic activity. Atrial hypocontractility plays a major role in the formation of atrial thrombi that lead to the occurrence of AF-related thromboembolic events. This study was aimed at elucidating the poorly understood molecular basis of atrial hypocontractility in AF.MethodsMembrane currents (whole-cell voltage-clamp technique), cytosolic calcium concentration [Ca]i (epifluorescence using Fluo-3 AM) and fractional shortening (Ionoptix) were measured simultaneously in right atrial myocytes from sinus rhythm (Ctl) and AF patients.ResultsL-type Ca current density and Ca transient amplitude (Δ[Ca]i) were 50% lower in AF than in Ctl, diastolic [Ca]i was unchanged (Figure, Panel A and B). Coupling efficiency between Ca influx and sarcoplasmic reticulum (SR) Ca release was comparable in Ctl and AF. SR Ca content calculated by integrating Na-Ca exchange current (INCX) during caffeine-induced release was similar in both groups. Atrial cardiomyocytes from patients with AF were ~30% longer compared to Ctl and the fractional shortening (ΔL/L0) of the myocytes in the AF group was impaired. Plotting fractional shortening vs. [Ca]i transient amplitude revealed a flatter curve in myocytes from AF patients pointing to impaired Ca-response of contractile proteins (Panel C). To determine intracellular Ca buffering, free [Ca]i- as determined from epifluorescent signal - was plotted against total [Ca]i, determined from integration of INCX during caffeine application (Panel D). Fitting hyperbolic buffering curves revealed a tendency to an increased Ca affinity (Kd) and impaired maximum buffering capacity (Bmax) in AF. The latter points to reduced availability of contractile proteins.ConclusionsBoth reduced SR Ca release due to decreased trigger ICa,L and impaired contractile response to systolic Ca-release, contribute to atrial hypocontractility in AF.