Con preghiera di diffusione tra tutti i possibili interessati, scusandomi per invii multipli. Cordialmente, Giacomo Aletti

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Nell'ambito dei Reading Group Seminars e del Seminario di Matematica Applicata, il giorno lunedì 1 Dicembre 2014, alle ore 14.30, nell'Aula C del Dipartimento di Matematica dell'Universita' degli Studi di Milano, Via C. Saldini, 50, Milano,

"Ionic mechanism underlying cardiac pacemaking: Insights from a mathematical model" Lara CHARAWI Dipartimento Matematica, Università di PAVIA

Abstract: The ionic mechanisms at the basis of the spontaneous pacemaker activity of sinoatrial node (SAN) cells is a matter of intense debate [1], in particular the role of the hyperpolarization-activated current, known as the "funny" current If [2]. Computational models of the electrical activity of SAN cells have been proposed to gain a deeper understanding of the phenomenon, however they fail in reproducing experimental effects of If modifications. We present a novel mathematical model of rabbit SAN action potential [3], developed by updating the description of membrane currents and intracellular mechanisms on the basis of experimental acquisitions, in an attempt to reproduce pacemaker activity and its physiological and pharmacological modulation. Our model describes satisfactorily experimental data on pacemaking regulation due to neural modulation, If block and inhibition of the intracellular calcium handling. Simulation results suggest that a detailed description of the intracellular calcium fluxes is fully compatible with the observation that If is a major component of pacemaking and rate modulation.

Keywords Cardiac modelling, cardiac pacemaking, sinoatrial node, funny current, autonomic rate modulation.

References [1] Lakatta, E. G., and DiFrancesco, D. (2009). What keeps us ticking: a funny current, a calcium clock, or both?. J. mol. cell. cardiol., 47(2), 157-170. [2] Brown, H. F., DiFrancesco, D., and Noble, S. J. (1979). How does adrenaline accelerate the heart? Nature, 280, 235-236. [3] Severi, S., Fantini, M., Charawi, L. A., and DiFrancesco, D. (2012). An updated computational model of rabbit sinoatrial action potential to investigate the mechanisms of heart rate modulation. J. physiol., 590(18), 4483-4499.

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Reading Group Seminars: The Reading Group Seminars (RGS) are organized within an open community of researchers interested in applying up to date mathematical modeling and data analysis approaches to the study of biological systems. The RGS take place at the Math. Department in Milan (via Saldini). Initiatives and updates are published on the website: http://rgs.mat.unimi.it/.