A Regional Reduction in Ito and IKACh in the Murine Posterior Left Atrial Myocardium Is Associated with Action Potential Prolongation and Increased Ectopic Activity.

BACKGROUND: The left atrial posterior wall (LAPW) is potentially an important area for the development and maintenance of atrial fibrillation. We assessed whether there are regional electrical differences throughout the murine left atrial myocardium that could underlie regional differences in arrhythmia susceptibility. METHODS: We used high-resolution optical mapping and sharp microelectrode recordings to quantify regional differences in electrical activation and repolarisation within the intact, superfused murine left atrium and quantified regional ion channel mRNA expression by Taqman Low Density Array. We also performed selected cellular electrophysiology experiments to validate regional differences in ion channel function. RESULTS: Spontaneous ectopic activity was observed during sustained 1Hz pacing in 10/19 intact LA and this was abolished following resection of LAPW (0/19 resected LA, P<0.001). The source of the ectopic activity was the LAPW myocardium, distinct from the pulmonary vein sleeve and LAA, determined by optical mapping. Overall, LAPW action potentials (APs) were ca. 40% longer than the LAA and this region displayed more APD heterogeneity. mRNA expression of Kcna4, Kcnj3 and Kcnj5 was lower in the LAPW myocardium than in the LAA. Cardiomyocytes isolated from the LAPW had decreased Ito and a reduced IKACh current density at both positive and negative test potentials. CONCLUSIONS: The murine LAPW myocardium has a different electrical phenotype and ion channel mRNA expression profile compared with other regions of the LA, and this is associated with increased ectopic activity. If similar regional electrical differences are present in the human LA, then the LAPW may be a potential future target for treatment of atrial fibrillation

Exciton-polariton topological insulator

The authors thank R. Thomale for fruitful discussions. S.K. acknowledges the European Commission for the H2020 Marie Skłodowska-Curie Actions (MSCA) fellowship (Topopolis). S.K., S.H. and M.S. are grateful for financial support by the JMU-Technion seed money program. S.H. also acknowledges support by the EPSRC ”Hybrid Polaritonics” Grant (EP/M025330/1). The Würzburg group acknowledges support by the ImPACT Program, Japan Science and Technology Agency and the State of Bavaria. T.C.H.L. and R. G. were supported by the Ministry of Education (Singapore) Grant No. 2017-T2-1-001Topological insulators—materials that are insulating in the bulk but allow electrons to flow on their surface—are striking examples of materials in which topological invariants are manifested in robustness against perturbations such as defects and disorder1. Their most prominent feature is the emergence of edge states at the boundary between areas with different topological properties. The observable physical effect is unidirectional robust transport of these edge states. Topological insulators were originally observed in the integer quantum Hall effect2 (in which conductance is quantized in a strong magnetic field) and subsequently suggested3,4,5 and observed6 to exist without a magnetic field, by virtue of other effects such as strong spin–orbit interaction. These were systems of correlated electrons. During the past decade, the concepts of topological physics have been introduced into other fields, including microwaves7,8, photonic systems9,10, cold atoms11,12, acoustics13,14 and even mechanics15. Recently, topological insulators were suggested to be possible in exciton-polariton systems16,17,18 organized as honeycomb (graphene-like) lattices, under the influence of a magnetic field. Exciton-polaritons are part-light, part-matter quasiparticles that emerge from strong coupling of quantum-well excitons and cavity photons19. Accordingly, the predicted topological effects differ from all those demonstrated thus far. Here we demonstrate experimentally an exciton-polariton topological insulator. Our lattice of coupled semiconductor microcavities is excited non-resonantly by a laser, and an applied magnetic field leads to the unidirectional flow of a polariton wavepacket around the edge of the array. This chiral edge mode is populated by a polariton condensation mechanism. We use scanning imaging techniques in real space and Fourier space to measure photoluminescence and thus visualize the mode as it propagates. We demonstrate that the topological edge mode goes around defects, and that its propagation direction can be reversed by inverting the applied magnetic field. Our exciton-polariton topological insulator paves the way for topological phenomena that involve light–matter interaction, amplification and the interaction of exciton-polaritons as a nonlinear many-body system.PostprintPeer reviewe