IDENTIFICATION OF A GENE ENCODING A HYPERPOLARIZATION-ACTIVATED PACEMAKER CHANNEL OF BRAIN

The generation of pacemaker activity in heart and brain is mediated by hyperpolarization-activated cation channels that are directly regulat ed by cyclic nucleotides. We previously cloned a novel member of the v oltage-gated K channel family from mouse brain (mBCNG-1) that containe d a carboxy-terminal cyclic nucleotide-binding domain (Santoro et al., 1997) and hence proposed it to be a candidate gene for pacemaker chan nels. Heterologous expression of mBCNG-1 demonstrates that it does ind eed code for a channel with properties indistinguishable from pacemake r channels in brain and similar to those in heart. Three additional mo use genes and two human genes closely related to mBCNG-1 display uniqu e patterns of mRNA expression in different tissues, including brain an d heart, demonstrating that these channels constitute a widely express ed gene family.