Fig. 7.

Lead ions enhance the fast voltage-dependent inactivation of cardiac Cav1.2 channels expressed in tsA 201 cells. a A pulse protocol to study the shift of charge distribution promoted by inactivating–conditioning pulses of different lengths of time. The pulse shown with a horizontal arrow on top corresponds to the inactivating-conditioning pulse of varying duration (Tc). After conditioning, a test pulse was applied to record the gating currents. A very short interpulse to − 40 mV was applied to mimick the conditions used to study ICa in isolated cardiomyocytes. The procedure was done in control and in 30 μM Pb²⁺. b Gating current recordings obtained in control Tyrode’s solution (black traces) and in Tyrode’s solution plus 30 μM Pb²⁺ (gray traces). The recordings in the upper panel are superimposed with a low temporal gain. Lower panel, the same recording is shown with the OFF trace at a higher temporal resolution. The area under the gating currents corresponds to the charge movement obtained at that particular test pulse. c A plot of half-voltage activation (V_1/2) versus conditioning time length (T_c). For each duration of conditioning voltages an entire charge distribution was used, and the half-voltage activation (V_1/2) was obtained by the best fit of a Boltzmann distribution. The procedure was repeated for different conditioning lengths of time in control and in 30 μM Pb²⁺. The solid lines correspond to biexponential fits in control (black) and in 30 μM lead (dark gray). The half-activation potential (V_1/2) is shifted towards more negative values by conditioning the pulse more rapidly in the presence of 30 μM Pb²⁺ than in controls. This result suggests that extracellular lead promotes fast VDI in cardiac Cav1.2 channels