PRIMARY STRUCTURE AND FUNCTIONAL EXPRESSION OF A CGMP-GATED POTASSIUMCHANNEL

Cyclic nucleotides modulate potassium (K) channel activity in many cel ls and are thought to act indirectly by inducing channel protein phosp horylation. Herein we report the isolation from rabbit of a gene encod ing a K channel (Kcn1) that is specifically activated by cGMP and not by cAMP. Analysis of the deduced amino acid sequence (725 amino acids) indicates that, in addition to a core region that is highly homologou s to Shaker K channels, Kcn1 also contains a cysteine-rich region simi lar to that of ligand-gated ion channels and a cyclic nucleotide-bindi ng region. Northern blot analysis detects gene expression in kidney, a orta, and brain. Kcn1 represents a class of K channels that may be spe cifically regulated by cGMP and could play an important role in mediat ing the effects of substances, such as nitric oxide, that increase int racellular cGMP.