1. Stefano Severi C 3 MIG 7 maggio 2009

2. Introduzione It is well known that changes in serum calcium influence the cardiac electrical activity particularly affecting ventricular repolarization The primary electrocardiographic manifestation of hypocalcaemia is QTc prolongation, which is associated with increased risk of early after-depolarizations and triggered arrhythmias hypercalcaemia exerts an opposite effect on the ECG with the hallmark of abnormal shortening of the QTc interval

3. Introduzione Ca 2+ -dependency of repolarization is particularly relevant in dialysis, when plasma Ca 2+ levels may vary widely During dialysis, QTc was found to inversely correlate with plasma Ca 2+

4. 4 RELATION BETWEEN CALCIUM CONCENTRATION AND ACTION POTENTIAL (AP) Calcium currents influence the plateau duration: in particular the QT interval increases when decreasing [Ca 2+ ] is observed.

5. Copyright ©2005 American Heart Association Bai, C.-X. et al. Circ Res 2005;96:64-72 Effects of rise in [Ca 2+ ] o on APD Background

6. The aim of the present study was to identify the ionic mechanism/s likely to underlie the APD dependency on [Ca2+]o by using an in silico approach. To this purpose, new formulations of the Ca2+- dependency of IKs, IKr and ICaL were incorporated in the TNNP model of the human ventricular AP Aim

7. Methods Ten Tusscher human ventricular model (Am J Physiol Heart Circ Physiol 2004) [Ca 2+ ] o ranging from 1 to 3 mM was analysed

8. Metodi

13. Figure 10. Influence of [Ca 2+ ] i homeostasis on L-type Ca 2+ current, charge transfer and L-type channel inactivation (f AP ) during an action potential with an overshoot of 50 mV The panels show from top to bottom: command voltage, matching averaged 100 µM Cd 2+ -sensitive currents, averaged charge transfers, and averaged f AP values plotted as function of time. A, effect of buffering [Ca 2+ ] i with 10 mM EGTA (, n = 9) or 10 mM BAPTA (, n = 14). Recordings were obtained from different cells. B, effect of inhibition of the SR by 1 µM ryanodine and 1 µM thapsigargin (, n = 19), and of blocking Na + -Ca 2+ exchange by rapidly substituting Li + for Na + in the external solution (, n = 8). Recordings were made on different cells. The data recorded under control conditions (, n = 24) are redrawn from Figs 3 and 5 to allow comparison of the results. Significance of difference from control values was tested using Student's t test (* P < 0·05; ** P < 0·01). LINZ & MEYERTEN TUSSCHER GRANDI & SEVERI

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17. we have shown (Fig. 6) that the AP prolongs as the store is depleted and shortens as the SR is refilled with Ca2+ in about 20 beats. A similar time course has been shown experimentally [47]: after removal of caffeine (which empties the SR, suppresses the Ca2+ transient and prolongs the AP), the APD is gradually shortened to basal length in parallel with the restoration of the magnitude of the Ca2+ transient during the refilling of the SR [49] as the rat cardiomyocytes are stimulated.

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21. Ringraziamenti