Use-dependent inhibition of hHCN4 by ivabradine and relationship with reduction in pacemaker activity.

Background And Purpose: Ivabradine, a specific and use-dependent I(f) inhibitor, exerts anti-ischaemic activity purely by reducing heart rate. The aim of this work was to characterize its effect on the predominant HCN channel isoform expressed in human sino-atrial nodes (hSAN), to determine its kinetics in HCN channels from multicellular preparations and rate-dependency of its action.

Experimental Approach: RT-PCR analysis of the four HCN channel isoforms was carried out on RNAs from hSAN.