L-type calcium current in human ventricular myocytes at a physiological temperature from children with tetralogy of Fallot

Objective: The aim was to investigate the electrophysiological properties of the L-type calcium current ( I Ca,L) in ventricular myocytes at a physiological temperature (36–37°C) isolated from children undergoing surgical repair of tetralogy of Fallot. Methods: I Ca,L was recorded with the patch-clamp technique in the single electrode whole-cell mode at a physiological calcium concentration (1.8 mmol/l) at 36–37°C. Results: Under these conditions, maximum current density averaged −5.80±0.45 pA/pF. I Ca,L showed a bell-shaped current–voltage relationship: the current activated at −37.7±1.36 mV, peaked at +9.41±1.60 mV and reversed at +57.7±2.12 mV ( n =17). At +10 mV, time to peak of I Ca,L was 5.23±0.46 ms. Membrane potentials for half-maximal steady-state activation and inactivation of I Ca,L were −6.02 and −20.4 mV, respectively, the slope factors were 7.16 mV for steady-state activation and 6.49 mV for steady-state inactivation. I Ca,L did not completely inactivate and showed a big window current between −45 and +40 mV. The inactivation of I Ca,L showed a biexponential time course with a fast time constant ranging from 9.11 to 12.9 ms and a slow time constant ranging from 60.9 to 220 ms between −30 and +30 mV. Only the slow time constant showed a pronounced voltage dependency. The recovery from inactivation of I Ca,L was biphasic with a fast time constant of 60.7 ms and a slow time constant of 619 ms. β-Adrenergic stimulation with isoprenaline (1 μmol/l) increased the I Ca,L density from −5.71±1.55 to −13.8±1.96 pA/pF (142%; P <0.05) at +10 mV. Conclusions: The present study demonstrates that most of the electrophysiological properties of I Ca,L in ventricular myocytes isolated from children with tetralogy of Fallot resemble those of adult ventricular cells. The existence of a big calcium window current could be involved in the occurrence of early afterdepolarizations which could lead to the high incidence of arrhythmias after surgical repair of tetralogy of Fallot.