The HCN gene family: molecular basis of the hyperpolarization-activated pacemaker channels

The molecular basis of the hyperpolarization-activated cation channels that underlie the anomalous rectifying current variously termed Ih, Iq, or I(f) is discussed. On the basis of the expression patterns and biophysical properties of the newly cloned HCN ion channels, an initial attempt at defining the identity and subunit composition of channels underlying native Ih is undertaken. By comparing the sequences of HCN channels to other members of the K channel superfamily, we discuss how channel opening may be coupled to membrane hyperpolarization and to direct binding of cyclic nucleotide. Finally, we consider some of the questions in cardiovascular physiology and neurobiology that can be addressed as a result of the demonstration that Ih is encoded by the HCN gene family.