Figure 4. HCN4 and HCN1 currents are blocked by ivabradine according to the protocol used to activate them.

A, left, I_HCN4 records in control (cont) and after full block by 3 μ m ivabradine induced by a standard activation/deactivation protocol at −100/+5 mV (as in Fig. 1); steady-state block was 60.9%. A, right, action of the same drug concentration when applied during steady-state I_HCN4 activation at −100 mV; this protocol caused a block of 8.0%. B, similar experiments in an HCN1-expressing cell exposed to 1 μ m ivabradine resulted in a 50.8% block of I_HCN1 with the pulsing protocol (left) and in no blocking effect when the same drug concentration was applied during steady-state I_HCN1 activation at −100 mV (right).