Cardiac pacemaking is controlled by an inward current called If, which is activated by membrane hyperpolarization of pacemaker cells in the sinoatrial node. Recently, a family of hyperpolarization-activated and cyclic nucleotide-gated cation(HCN) channels comprising at least four members (HCN1－HCN4) has been cloned. Two of these channels, HCN2 and HCN4, are expressed in the heart. When expressed in heterologous cells, HCN2 and HCN4 reveal general features of native If. In the present review we describe the molecular diversity and functional expression of the HCN channels and discuss structural determinants of the channels.
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