Abstract
Nitric oxide (NO) is a gaseous signaling molecule, having diverse biological actions. In addition to the well-known guanylate cyclase/cGMP/protein kinase G pathway, direct protein s-nitrosylation and s-glutathiolation provide a novel mechanism of NO-dependent signaling. In cardiac myocytes, the slowly activating delayed rectifier potassium current (IKs) channels appear to co-localize with NO synthase-3 (NOS3) in caveolae (ref 1), and is a target of s-nitrosylation by NO (ref 2). S-nitrosylation by NO underlies physiologically important regulatory mechanisms of IKs by cytosolic Ca2+ and by sex hormones. Rise in intracellular Ca2+ activates NOS3 and produces NO via a Ca2+/calmodulin-dependent pathway, resulting in activation of IKs channel (ref 3). Sex hormones, such as testosterone, estradiol, and progesterone, activate NOS3 via their non-genotropic pathway, which also enhances IKs (ref 4). It has been shown that scaffolding proteins belonging to striatin family (striatin, zinedin, and SG2NA) compose macromolecular complex involving caveolin, calmodulin, NOS, and sex hormone receptor. Dynamic changes in protein-protein interaction around this macromolecular complex play an important role in NO-dependent IKs regulation. [References] (1) J. Biol. Chem. 2004;279:40778-40787.(2) Br. J. Pharmacol. 2004;142:567-575.(3) Circ. Res. 2005;96:64-72.(4) Circulation (in revision). [Jpn J Physiol 55 Suppl:S6 (2005)]
